Methods of treating acne and rosacea with galvanic generated electricity

ABSTRACT

The present invention features a method of treating acne or rosacea on the skin by applying electricity to skin in need of such treatment wherein said electricity is generated by a first conductive electrode in electric communication with a second conductive electrode, wherein both the first conductive electrode and the second conductive electrode are in ionic communication with the skin, wherein the difference of the standard potentials of the first conductive electrode and the second conductive electrode is at least 0.2 V and wherein the electrons that pass between the first conductive electrode and the second conductive electrode are generated as a result of such difference of the standard potentials.

CROSS REFERENCE TO RELATED APPLICATIONS

This is a continuation-in-part of co-pending application Ser. No.10/685,282, filed on Oct. 14, 2003, which a continuation-in-part ofco-pending application Ser. No. 10/609,727, filed on Jun. 30, 2003,which are hereby incorporated by reference in its entirety.

BACKGROUND OF THE INVENTION

Using a galvanic couple as the power source in iontophoresis device iswell known in the art. See e.g., U.S. Pat. Nos. 5,147,297, 5,162,043,5,298,017, 5,326,341, 5,405,317, 5,685,837, 6,584,349, 6,421,561 and6,653,014. Typical materials from which a galvanic couple is madeincludes a zinc donor electrode and a silver chloride counter electrode.Such a combination produces an electric potential of about one volt.Such a galvanic couple powered iontophoresis system, absent somecontrolling means, activates automatically when body tissue and/orfluids form a complete circuit with the system to generate theelectricity.

SUMMARY OF THE INVENTION

In one aspect, the present invention features a method of treating acne,rosacea, and/or wounds and/or reducing the appearance of pigmentation byapplying electricity to a barrier membrane in need of such treatmentwherein the electricity is generated by a first conductive electrode inelectric communication with a second conductive electrode, wherein boththe first conductive electrode and the second conductive electrode arein ionic communication with the barrier membrane, wherein the differenceof the standard potentials of the first conductive electrode and thesecond conductive electrode is at least 0.2 V and wherein the electronsthat pass between the first conductive electrode and the secondconductive electrode are generated as a result of such difference of thestandard potentials.

In another aspect, the present invention features a method of promotinga product including a topical carrier, a first conductive electrode inthe form of a particulate, and a second composition comprising secondconductive electrode in the form of a particulate wherein the differenceof the standard potentials of the first conductive electrode and thesecond conductive electrode is at least 0.2 V, such method includingpromoting the topical application of such composition for the treatmentof acne, rosacea, and/or wounds, and/or reducing the appearance ofpigmentation.

In another aspect, the present invention features a method ofadministering an active agent to a human barrier membrane by applying tothe membrane a device including a housing having the barrier membranecontacting surface, a first conductive electrode, a second conductiveelectrode, and a carrier containing the active agent; wherein the firstconductive electrode is in electric communication with the secondconductive electrode, wherein the first conductive electrode and thesecond conductive electrode are in ionic communication with the carrier,and wherein the carrier is in communication with the barrier membranethrough the barrier membrane contacting surface, wherein the differenceof the standard potentials of the first conductive electrode and thesecond conductive electrode is at least 0.2 V and wherein the electronsthat pass between the first conductive electrode and the secondconductive electrode are generated as a result of such difference of thestandard potentials.

In another aspect, the present invention features a method ofadministering an active agent to a human barrier membrane by topicallyapplying a composition to such membrane, the composition including theactive agent, a first conductive electrode in the form of a particulateand a second conductive electrode in the form of a particulate, whereinthe difference of the standard potentials of the first conductiveelectrode and the second conductive electrode is at least 0.2 V.

Other features and advantages of the present invention will be apparentfrom the detailed description of the invention and from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a cross-sectional view of one embodiment of the galvaniccouple powered device suitable for practicing the invention. Theconductive electrodes 140 and 240 are connected respectively by the leadwires 110 and 210 to electrically insulated connecting wire 350 locatedat the back of the device 500.

FIG. 2 is a cross-sectional view of one embodiment of the galvaniccouple powered device suitable for practicing the invention. Theconductive electrodes 140 and 240 are connected respectively by the leadwires 110 and 210 to electrically insulated connecting wire 350 embeddedin the carrier layer 120 of the device 500.

FIG. 3 is a cross-sectional view of one embodiment of the galvaniccouple powered device suitable for practicing the invention. Theconductive electrodes 140 and 240 are connected respectively by the leadwires 110 and 210 to electrically insulated connecting wire 350 embeddedin the carrier layer 120.

FIG. 4 is a cross-sectional view of one embodiment of the galvaniccouple powered device suitable for practicing the invention. Theconductive electrodes 140 and 240 are in electric communication witheach other by direct connection. The two conductive electrodes forms agalvanic couple which is in contact with the carrier layer 120.

FIG. 5 is a cross-sectional view of one embodiment in accordance withthe invention. The device 800 contains two electrode assemblies 200 and600.

FIG. 6 is a top view of one embodiment in accordance with the inventionshowing the conductive electrodes 140 and 240 connected by electricallyinsulated connecting wire 350 embedded in the carrier layer 120. Theconductive electrodes 140 and 240 are arranged in an inter-digitatedconfiguration.

FIG. 7 is a top view of one embodiment in accordance with the inventionshowing the conductive electrodes 140 and 240 connected by electricallyinsulated connecting wire 350 embedded in the carrier layer 120. Theconductive electrodes 140 and 240 are arranged in a concentricconfiguration.

FIG. 8 is a top view of one embodiment in accordance with the inventionshowing a plurality of sets of conductive electrodes 140 and 240connected to each other by connecting wire 350 to form a plurality ofgalvanic couple power sources, which are in contact with the carrierlayer 120. The conductive electrodes 140 and 240 are arranged in aparallel configuration.

FIG. 9 is a top view of one embodiment in accordance with the inventionshowing a plurality of sets of conductive electrodes 140 and 240connected to each other by a direct physical contact at intersections370 to form a plurality of galvanic couple power sources, which are incontact with the carrier layer 120. The conductive electrodes 140 and240 are arranged in a perpendicular configuration.

FIG. 10 is a top view of one embodiment in accordance with the inventionshowing the conductive electrodes 140 and 240 connected by electricallyinsulated connecting wire 350 embedded in the carrier layer 120.

FIG. 11 is a top view of one embodiment in accordance with the inventionshowing the conductive electrodes 140 and 240 embedded in the carrierlayer 120.

DETAILED DESCRIPTION OF THE INVENTION

It is believed that one skilled in the art can, based upon thedescription herein, utilize the present invention to its fullest extent.The following specific embodiments are to be construed as merelyillustrative, and not limitative of the remainder of the disclosure inany way whatsoever.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which the invention belongs. Also, all publications, patentapplications, patents, and other references mentioned herein areincorporated by reference. Unless otherwise indicated, a percentagerefers to a percentage by weight (i.e., % (W/W)).

What is meant by a “product” is a product containing the device infinished packaged form. In one embodiment, the product containsinstructions directing the user to apply the device to the barriermembrane (e.g., to treat a skin condition). Such instructions may beprinted on the device, label insert, or on any additional packaging.

In one aspect, the present invention features promoting a device of thepresent invention for its intended use. What is meant by “promoting” ispromoting, advertising, or marketing. Examples of promoting include, butare not limited to, written, visual, or verbal statements made on theproduct or in stores, magazines, newspaper, radio, television, internet,and the like.

As used herein, “pharmaceutically-acceptable” means that the ingredientswhich the term describes are suitable for use in contact with thebarrier membrane (e.g., the skin or mucosa) without undue toxicity,incompatibility, instability, irritation, allergic response, and thelike.

As used herein, “safe and effective amount” means an amount of theingredient or of the composition sufficient to provide the desiredbenefit at a desired level, but low enough to avoid serious sideeffects. The safe and effective amount of the ingredient or compositionwill vary with the area being treated, the age and skin type of the enduser, the duration and nature of the treatment, the specific ingredientor composition employed, the particular pharmaceutically-acceptablecarrier utilized, and like factors.

As used herein, the term “treatment” means the treatment (e.g.,alleviation or elimination of symptoms and/or cure) and/or prevention orinhibition of the condition (e.g., a skin condition). What is meant by a“skin condition” is a dermatological disease or disorder (including, butnot limited, acne, rosacea, or skin infections) or skin characteristic(including, but not limited to, pigmentation, hair growth regulation,skin texture, skin firmness, skin elasticity, skin vasculature, darkcircles, cellulite, sebum regulation, and skin shine). Examples of skininfections include, but are not limited to, those due to susceptiblepathogens such as acne, rosacea, impetigo, folliculitis, furunculosis,ecthyma, eczema, psoriasis, atopic dermatitis, herpes, epidermolysisbullosa, icthyosis, and infected traumatic lesions (e.g., ulcers, minorburns, cuts, abrasions, lacerations, wounds, biopsy sites, surgicalincisions and insect bites).

The present invention relates to a device for the delivery ofelectricity (e.g., to induce a desirable biological response) and/or anactive agent into a barrier membrane. In one embodiment, the device ofthe present invention is a self-contained device containing at least apair of two dissimilar conductive electrodes in electric communicationas a power source. By “electric communication” is meant that electronscan directly pass between the elements of the device (e.g., between theconductive electrode of the device). In one embodiment, the twoconductive electrodes are in electric communication via direct contactwith each other.

By “ionic communication” it meant that electrons can pass between theelements (e.g., the conductive electrode, the carrier and/or theconductive electrode and the skin) through the migration of ions as“electron movers” in contact with such elements (e.g., electrons passbetween the conductive electrode and the skin via ionic transport ofelectrolytes (e.g., in the carrier) in contact with the conductiveelectrode and the skin).

In one embodiment, the two conductive electrodes are in ioniccommunication with the carrier containing an electrolyte (e.g., ions ofone or more electrolytes in the carrier are in contact with theconductive electrode) and the carrier is in ionic communication with theskin. This electrode configuration differs from those in conventionaliontophoresis devices in which each conductive electrode is in contactwith a separate carrier (e.g., each electrode is contained in a separatecompartment and affixed to the skin with electric insulation betweenthem in order that all the electric current travels through the skin tocomplete the electric circuit). An advantage of such an embodiment ofthe present invention includes the capability of deliveringsimultaneously active agents of opposite charges from the same carrierinto substantially the same skin site under the conductive electrodes.Another advantage is that the devices of the present invention are mucheasier to manufacture than conventional iontophoresis devices, andtherefore, are enable substantial cost-savings.

The device contains a barrier membrane contacting surface (e.g., a skincontacting surface) that is applied to the membrane (e.g., applied bythe user to the user's skin). The device is arranged such that carrieris in communication with the barrier membrane contacting surface (e.g.,such that electricity and/or the active agent may be administered fromthe carrier into the barrier membrane). In one embodiment, the carrieris the barrier membrane contacting surface (e.g., the carrier is ahydrogel). In one embodiment, the device contains a light emitting diodesuch that light from the light emitting diode is in communication withthe barrier membrane contacting surface (e.g., such that the light maybe administered to the barrier membrane).

In one embodiment, the device of the present invention delivers anactive agent into the barrier membrane. The active agents to bedelivered by the device of the present invention include active agentseither initially incorporated in the carrier or electrochemicallygenerated by the electric current passing from a conductive electrodethrough the carrier during use. What is meant by “electrochemicallygenerated” is that the chemical specie is created as a result of anelectrochemical reaction resulting from electric current flowing throughan electrode, such a chemical specie released from a reactive electrode(e.g., an electrochemically generated zinc ion), a chemical specieelectrochemically generated on the surface of an inert electrode, or achemical specie that is a subsequent reaction product of suchelectrochemically generated specie.

Galvanic Couple

The device/composition of the present invention has a galvanic couple asits power source, wherein the electrons that pass between the firstconductive electrode and the second conductive electrode are generatedas a result of the difference of the standard potentials between theelectrodes (e.g., the electricity is not generated by an externalbattery or other power source such as an AC power source). Examples ofsuch galvanic couples include, but are not limited to, zinc-copper,zinc-copper/copper halide, zinc-copper/copper oxide, magnesium-copper,magnesium-copper/copper halide, zinc-silver, zinc-silver/silver oxide,zinc-silver/silver halide, zinc-silver/silver chloride,zinc-silver/silver bromide, zinc-silver/silver iodide,zinc-silver/silver fluoride, zinc-gold, magnesium-gold, aluminum-gold,magnesium-silver, magnesium-silver/silver oxide, magnesium-silver/silverhalide, magnesium-silver/silver chloride, magnesium-silver/silverbromide, magnesium-silver/silver iodide, magnesium-silver/silverfluoride, magnesium-gold, aluminum-copper, aluminum-silver,aluminum-silver/silver oxide, aluminum-silver/silver halide,aluminum-silver/silver chloride, aluminum-silver/silver bromide,aluminum-silver/silver iodide, aluminum-silver/silver fluoride,copper-silver/silver halide, copper-silver/silver chloride,copper-silver/silver bromide, copper-silver/silver iodide,copper-silver/silver fluoride, iron-copper, iron-copper/copper oxide,iron-copper/copper halide, iron-silver, iron-silver/silver oxide,iron-silver/silver halide, iron-silver/silver chloride,iron-silver/silver bromide, iron-silver/silver iodide,iron-silver/silver fluoride, iron-gold, iron-conductive carbon,zinc-conductive carbon, copper-conductive carbon, magnesium-conductivecarbon, and aluminum-carbon. The materials which serve to make up thegalvanic couple may also serve as the conductive electrodes of thedevice, e.g., zinc as the conductive anode and silver/silver chloride asthe conductive cathode or zinc as the conductive anode and copper as theconductive cathode. The metals serve as the galvanic couple andconductive electrodes may also be alloys. Non-limiting examples of thealloys include alloys of zinc, copper, aluminum, magnesium as anodematerials, and alloys of silver, copper, gold as cathode materials.

In one embodiment, the materials that make up the galvanic couple have astandard potential difference equal to or greater than about 0.1 volts,such as greater than about 0.2 volts such as greater than about 0.5volts. In one embodiment, the materials that make up the galvanic couplehave a standard potential difference equal to or less than about 3volts.

In one embodiment, the device or composition of the present inventiongenerates and/or is capable of generating current into the barriermembrane of from about 1 nano-A/cm² to about 400 micro-A/cm² ofelectricity such as from about 100 A/cm² to about 50 micro A/cm².

In one embodiment, one of the conductive electrodes is in the form of ametal sheet, a metal wire, or a metal coated on a substrate, and theother conductive electrode is attached or deposited to the firstconductive electrode. In a further embodiment, the metal sheet isperforated. In one embodiment, such perforated metal sheet is in theform of a mesh such as a mesh of zinc, magnesium, aluminum, copper, ortheir alloys thereof. In one embodiment, the second conductive electrodeis in the form a fabric coated with a metal, and its oxide, halide, andsulfide, such as a fabric coated with silver, silver/silver oxide,silver/silver halide, zinc, magnesium, copper, copper/copper halide,copper/copper oxide. In another embodiment, the second conductiveelectrode is deposited to the first conductive electrode by chemical orelectrochemical deposition such as electroless plating for chemicaldeposition and electroplating for electrochemical deposition as known inthe art. In a further embodiment, the second conductive electrode isdeposited to the first conductive electrode by physical deposition, suchas spray coating, plasma coating, conductive ink coating, screenprinting, dip coating, or vacuum deposition.

In one embodiment, the device is a single compartment treatment device.What is meant by a “single compartment treatment device” is a device inwhich both conductive electrodes of the device are in contact with thesame carrier. Examples of such devices are shown in FIGS. 1–4 and 6–11.

Carrier

The carrier of the present invention is a liquid (e.g., a solution, asuspension, or an emulsion which may be immobilized within an absorbentmaterial such as gauze or non-woven pad), a semi-solid (e.g., a gel, acream, a lotion, microemulsion, or hydrogel), or a solid (e.g., alyophilized composition containing active agents, which may bereconstituted by adding a liquid prior to use) that during use iscapable of conducting electricity from a conducting electrode (e.g., thecarrier contains one or more electrolytes, organic solvents, and water).In one embodiment, the carrier (e.g., a liquid or semi-solid) is addedto the device by the user prior to applying the device to the barriermembrane.

Examples of electrolytes include, but are not limited to,pharmaceutically acceptable organic and organic salts and buffers.Examples of salts include, but are not limited to, chloride salts (suchas sodium chloride, potassium chloride, lithium chloride, calciumchloride, strontium chloride, magnesium chloride or other chloridesalts), as well as salts of sodium, potassium, lithium, calcium,magnesium, strontium, fluoride, iodide, bromide. Examples of buffersinclude, but are not limited to, phosphates, citrates, acetates,lactates, and borates.

In one embodiment, the electrolyte is an active agent, or becomes anactive agent after the passage of the electric current through thecarrier. Examples of such electrolyte-active agents include, but are notlimited to, salicylic acid, salicylates, and other weak acid or weakbase active agents.

In one embodiment, the carrier contains water. In a further embodiment,the carrier may also contain one or more organic solvents. Examples oforganic solvents include, but are not limited to: dimethyl isosorbide;isopropylmyristate; surfactants of cationic, anionic and nonionicnature; vegetable oils; mineral oils; waxes; gums; synthetic and naturalgelling agents; alkanols; glycols; and polyols.

Examples of glycols include, but are not limited to, glycerin, propyleneglycol, butylene glycol, pentalene glycol, hexylene glycol, polyethyleneglycol, polypropylene glycol, diethylene glycol, triethylene glycol,glycerol, and hexanetriol, and copolymers or mixtures thereof. Examplesof alkanols include, but are not limited to, those having from about 2carbon atoms to about 12 carbon atoms (e.g., from about 2 carbon atomsto about 4 carbon atoms), such as isopropanol and ethanol. Examples ofpolyols include, but are not limited to, those having from about 2carbon atoms to about 15 carbon atoms (e.g., from about 2 carbon atomsto about 10 carbon atoms) such as propylene glycol.

The organic solvents may be present in the carrier in an amount, basedupon the total weight of the carrier, of from about 1 percent to about90 percent (e.g., from about 5 percent to about 50 percent). Water maybe present in the carrier (prior to use) in an amount, based upon thetotal weight of the carrier, of from about 5 percent to about 95 percent(e.g., from about 50 percent to about 90 percent).

The carrier may also contain: preservatives (such as cresol,chlorocresol, benzyl alcohol, methyl p-hydroxylbenzoate, propylp-hydroxybenzoate, phenol, thimerosal, benzalkonium chloride,benzethonium chloride, and phenylmercuric nitrate); stabilizing agentsor antioxidants (such as ascorbic acid, ascorbic acid esters,butylhydroxy anisole, butylhydroxy toluene, cysteine, N-acetylcysteine,sodium bisulfite, sodium metabisulfite, sodium formaldehydesulfoxylate,acetone sodium bisulfite, tocopherols, and nordihydroguaiaretic acid);chelating agents (such as ethylenediaminetetraacetic acid and itssalts); buffers (such as acetic acid, citric acid, phosphoric acid,glutamic acid, and salts thereof); and tonicity adjusting agents (suchas sodium chloride, sodium sulfate, dextrose and glycerin).

In one embodiment, the carrier may also contain a suspending materialand/or a fluid-absorbing material (e.g., for physically stabilizing theingredients of the carrier). Examples of suspending materials include,but are not limited to: cotton-based gauze; non-woven pads made of rayonor a mixture of rayon, polyester and/or other polymer fibers; open-cellfoam and sponge-like materials contained of polyurethane, polyesterand/or other polymers; and cross-linked and noncross-linked gellingmaterials, such as polyacrylamide, polyvinyl alcohol, gelatin,hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose,methylcellulose, and carboxymethylcellulose.

Examples of fluid-absorbing materials include, but are not limited to:cross-linked and non-cross-linked polymers; swellable polymers such aswater-swollen cellulose derivatives (e.g., methylcellulose (MC),hydroxyethyl methylcellulose (HEMA), hydroxypropyl methylkcellulose(HPMC), ethylhydroxyethyl cellulose (EHEC), hydroxyethylcellulose (HEC),hydroxypropylcellulose (HPC), and carboxymethlcellulose (CMC) and theirsalts); polyvinyl alcohol (PVA); polyvinylpyrrolidone (PVP);polyethylene oxide (PEO); polymers prepared by monomers such ashydroxyethyl methacrylate (HEMA), hydroxyethoxyethyl emthacrylate(HEEMA), hydroxydiethoxyethl methacrylate (HDEEMA), methyoxyethylmethacrylate (MEMA), methoxyethoxyethyl methacrylate (MEEMA),methyldiethoxyethyl methacrylate (MDEEMA), ethylene glycoldimethacrylate (EGDMA), n-vinyl-2pyrrolidone (NVP), methacrylic acid(MA), and vinyl acetate (VAC); polycrylamide; gelatin; gums andpolysaccharides such as gum arabic, gum karaya, gum tragacanth, guargum, gum benzoin, and alginic acid and their salts; polyethylene glycol(PEG); polypropylene glycol (PPG); and clays or other swellable mineralssuch as bentonite and montmorillonite. The amount of fluid absorbablematerial in the carrier may range from about 0.1% to about 95%, byweight, such as from about 1% to about 20%, by weight, of the carrier.

Another embodiment of the present invention is directed to pairing oneor more inert conductive electrodes in order to electrochemicallygenerate oxidizing or reducing agents from electrochemically reactivematerials in situ in the carrier. Such oxidizing or reducing agents canbe used as active agents to treat barrier membrane conditions.

Examples of the electrochemically reactive materials in the carrieraccording to the present invention include, but are not limited to,water and compounds containing the elements selected from the PeriodicTable of the Elements VIB and VIIB (such as oxygen, sulfur, fluorine,chlorine, bromine, and iodine).

In one embodiment, the reactive material reacts with the inert anode toform an oxidizing agent. Examples of such a reactive material includes,but is not limited to, the ions OH⁻, Cl⁻, I⁻, Br⁻, So₃ ²⁻, and HCO₃ ⁻.The present device, thus, enables to generation of oxidizing agents,such as nascent oxygen (e.g., singlet oxygen), chlorine and chlorinedioxide gases, which are difficult to formulate in a conventionaltopical product.

In one embodiment, the reactive material reacts with the inert cathodeto form a reducing agent. Examples of such a reactive material includes,but is not limited to, oxidized or disulfide forms of thio-compoundswith one or more sulfhydryl functional groups, thio-containing aminoacids and their salts or esters, and sulfides. Examples of suchthio-compounds include, but are not limited to: thioglycolic acid andits salts, such as thioglycolates of calcium, sodium, strontium,potassium, ammonium, lithium, magnesium, and other metal salts;thioethylene glycol; thioglycerol; thioethanol; thioactic acid; andthiosalicylic acid; and their salts. Examples of the thio-containingamino acids include, but are not limited to, L-cysteine, D-cysteine,DL-cysteine, N-acetyl-L-cysteine, DL-homocysteine, L-cysteine methylester, L-cysteine ethyl ester, N-carbamoyl cysteine, glutathione, andcysteamine. Examples of sulfides, include but are not limited to,calcium, sodium, potassium, lithium and strontium sulfides andglutathione disulfide. The inert cathode converts the aforementionedreactive oxidized or disulfide form of a sulfur-containing compound to athio-containing compound, or a sulfydryl-containing compound. Examplesof such a conversion is the conversion of cystine to cysteine and theconversion of the oxidized form of glutathione to glutathione.

In one embodiment, the concentration of the reactive material in thecarrier may range from about 0.01% to about 25%, by weight, such as fromabout 0.1% to about 10%, by weight, of the carrier. The pH value of thecarrier may range from about pH 1.5 to about pH 9, preferably from pH 2to pH 7, and most preferably from about pH 3 to pH 5.

In one embodiment, the carrier contains an adhesive. The adhesive isused to affix the device to the barrier membrane. Examples ofhydrophobic adhesives include, but are not limited to, silicones,polyisobutylenes and derivatives thereof, acrylics, natural rubbers, andcombinations thereof. Examples of silicone adhesives include, but arenot limited to, Dow Corning 355 available from Dow Corning of Midland,Mich.; Dow Corningo X7-2920; Dow Corning X7-2960; and GE 6574 availablefrom General Electric Company of Waterford, N.Y. Examples of acrylicadhesives include, but are not limited to, vinyl (D acetate-acrylate)multipolymers such as Gelva 7371, available from Monsanto Company of St.Louis, Mo.; Gelvao 7881; Gelva 2943; and 1-780 medical grade adhesiveavailable from Avery Dennison of Painesville, Ohio. Examples ofhydrophilic adhesives include, but are not limited to, gum papaya andother natural gums, MC, HEMA, HPMC, EHEC, HEC, HPC, CMC, PVA, PVP, PEO,HEMA, HEEMA, HDEEMA, MEMA, MEEMA, MDEEMA, EGDMA, NVP MA, VAC,polycrylamide. getatins, gum arabic, gum karaya, gum tragacanth, guargum, gum benzoin, and alginic acid and their salts, polyethylene glycol(PEG), and polypropylene glycol (PPG).

In one embodiment, the concentration of the adhesive in the carrier mayrange from about 0.1% to about 95%, by weight, such as from about 1% toabout 20%, by weight, of the carrier.

Electrodes

The conductive electrodes of the present invention may be a reactiveconductive electrodes or inert conductive electrodes. What is meant by a“reactive conductive electrode” is that the conductive electrode itselfgoes through a change in its chemical composition during the electrodechemical reactions occurring with the electric current passing throughthe electrode during the process. In one embodiment, the reactiveconductive electrode is an anode made of reactive materials such as apure metal or a metal alloy including, but not limited to, zinc,aluminum, copper, magnesium, manganese, silver, titanium, tin, iron, andalloys thereof. The materials which serve to make up the galvanic coupledescribed earlier may also serve as the reactive conductive electrode.Upon passage of an electric current, metal ions such as zinc, copper,magnesium, manganese and/or aluminum cations are released from the anodeinto the carrier and delivered into the barrier membrane. Such ions mayserve therapeutic benefits such as anti-microbial effects, immunologicmodulation, enzymatic regulation, and/or anti-inflammatory effects.

In one embodiment, the reactive conductive electrode is made of reactivematerials such as metal halides (e.g., silver-silver chloride (Ag/AgCl),silver-silver bromide, and silver-silver iodide). In this case, theprimary electrochemical reaction at the cathode surface is conversion ofsolid silver halide to metallic silver with little unwanted consumptionof the oxidizing agents generated by the anode. The released halide ionsmay be subsequently oxidized to oxidizing agents, such as chloride ionsto chlorine (Cl₂), hypochlorous acid (HClO), and hypochlorite ions(ClO⁻), and iodide ions to iodine.

What is meant by an “inert conductive electrode” is that the conductiveelectrode itself does not go through a change in its chemicalcomposition. In one embodiment, the anode is made of an inert conductiveelectrode, so that the electrochemical process at the surface of theanode generates oxidizing agents such as nascent oxygen (e.g., byelectrolysis of water) and/or chlorine-containing oxidizing agents suchas chlorine, hypochlorite, chlorate and perchlorate, and chlorinedioxide. Nascent oxygen is an oxidizing agent that is inhibitive to P.acnes, and chlorine-containing oxidizing agents are potent antimicrobialagent with bacteriacidal activity.

In one embodiment, the conductive electrode is made of, or coated on thesurface with, an inert materials such as noble metals (e.g., gold,platinum, or gold-coated conductive metals), conductive carbon (e.g.,glassy carbon or graphite), carbon-embedded polymers (e.g., carbonsilicone rubbers), conductive carbon polymer foam or sponge, silverhalide-coated silver (e.g., silver chloride-coated silver, silverbromide-coated silver, and silver iodide-coated silver), and corrosiveresistant alloys.

In one embodiment, the anode of the device, serving as the conductiveelectrode as well as a part of the galvanic couple power source, is madeof aforementioned reactive conductive oxidizable metals such as zinc,calcium, magnesium, aluminum, iron, tin, copper, or alloys thereof,while the cathode, also serving as the conductive electrode as well as apart of the galvanic couple power source, is made of the aforementionedreactive reducible conductive materials such as a more chemically stablemetal and its metal halides, oxide, sulfide or other metal salts, suchas silver and silver halides (e.g., silver chloride, silver bromide,silver iodide, silver fluoride), silver oxide, silver sulfide. In oneembodiment, the reducible conductive material is in direct contact witha good electric conductor, such as: a thin layer of silver chloride,silver oxide, or silver sulfide over metallic silver; silver chloridepowder with a binder (e.g., silver chloride ink); and/or silver chloridepowder mixed with silver or conductive carbon powder held together by abinder in a matrix form (e.g., silver-silver chloride ink and silverchloride-carbon ink).

In another embodiment, the anode of the device in the present inventionis made of aforementioned reactive conductive oxidizable metals whilethe cathode is made of aforementioned more chemically stable electrodematerials such as conductive carbon, metallic silver, gold or platinum,or a powder mixture of conductive carbon and the noble metal in a matrixform-as disclosed in U.S. Pat. No. 5,162,043.

In one embodiment, the device of the present invention enables thetargeted delivery of beneficial zinc through hair follicles to thepilosebaceous unit (i.e., a sebaceous gland and the associated hairfollicle) to treat acne or rosacea. Zinc is an essential metal to thehuman body because it participates in various biological activities inthe body (e.g., the body of a 70-Kg person contains about 2.3 grams ofzinc). It is known that the lack of zinc in the body may lead to skindiseases such as acne.

In another embodiment, the device of the present invention enables thetargeted delivery of other beneficial metals into the hair follicles andthe pilosebaceous glands by using an anode made of zinc alloy containingsmall quantities of other beneficial metals. Such beneficial metalsincludes, without limitation, certain metals essential to the human bodysuch asiron, copper, magnesium, manganese, calcium, potassium, aluminum,and selenium. As the zinc alloy anode oxidizes, it releases into thecarrier zinc ions and other beneficial metals in the zinc alloy, whichingredients subsequently migrate into the hair follicles under theapplied electric potential over the skin. In one embodiment, the contentof the zinc alloy in the anode is greater than about 50% by weight, suchas greater than 90% by weight.

In one embodiment, the ratio of the conductance measured between thefirst conductive and second conductive electrode of (i) the carrier and(ii) the skin hydrated with such carrier (wherein substantially all ofthe current passes between the electrodes through the skin) is in arange from about 10000:1 to about 1:100. In other words, the electriccurrent distribution between I_(carrier) and I_(skin) is such that thevalue of I_(carrier)/I_(skin) is between about 10,000 and about 0.01.I_(carrier) is the portion of the total current going through the device(I_(total)) that only passes through the carrier layer between the anodeand cathode without traveling through the skin, whereas I_(skin) is theportion of I_(total) that passes through the skin, namely,I_(total)=I_(carrier)+I_(skin).

Decreasing the ratio of the conductance of the carrier to theconductance of the skin will result in a greater percentage of currentpassage through the skin, thereby enhancing iontophoretic delivery ofany active agents being so delivered into the skin. Decreasing theconductivity of the carrier can nonexclusively be accomplished by addingless conductive materials to the carrier. Examples of such lessconductive materials include, but are not limited to, oils such assilicone or hydrocarbon oils, air pockets such as air bubbles or airpockets in a semi-solid carrier, or polymer or clay beads. In oneembodiment where the primary intention is to electrochemically generatespecies in the carrier, the value of I_(carrier)/I_(skin) is betweenabout 10,000 and about 1. In another embodiment where the primaryintention is to deliver electricity and/or active agents into the skin,the value of I_(carrier)/I_(skin) is between about 10 and about 0.01.Adjustment of the value of I_(carrier)/I_(skin) for a particularapplication can also be achieved by changing the distance between thefirst and the second electrode, or the distance between the twoconductive electrode and the skin. For example, as the distance betweenthe two conductive electrode decreases, the conductance measured betweenthe two electrode increases and so is the I_(carrier), leading to aincreased value of I_(carrier)/I_(skin). On the other hand, if thedistance between the two conductive electrodes and the skin increases,the I_(skin) increases, leading to decreased value ofI_(carrier)/I_(skin).

Active Agents

In one embodiment, the carrier contains one or more active agents. Whatis meant by an “active agent” is a compound (e.g., a synthetic compoundor a compound isolated from a natural source) that has a cosmetic ortherapeutic effect on the barrier membrane and the surrounding tissues(e.g., a material capable of exerting a biological effect on a humanbody) such as therapeutic drugs, including, but not limited to, organicand macromolecular compounds. Examples of such therapeutic drugs includepeptides, polypeptides, proteins, and nucleic acid materials comprisingDNA; and nutrients. Examples of polypeptide and protein active agentsinclude thyrotropin-releasing hormone (TRH), vasopressin,gonadotropin-releasing hormone (GnRH or LHRH), melanotropin-stimulatinghormone (MSH), calcitonin, growth hormone releasing factor (GRF),insulin, erythropoietin (EPO), interferon alpha, interferon beta,oxytocin, captopril, bradykinin, atriopeptin, cholecystokinin,endorphins, nerve growth factor, melanocyte inhibitor-I, gastrinantagonist, somatotatin, encephalins, melatonin, vaccines, botox(Botulinum neurotoxins), cyclosporin and its derivatives (e.g.,biologically active fragments or analogs). Other active agents includeanesthetics; analgesics (e.g., fentanyl and salts thereof such fentanylcitrate); drugs for treating psychiatric disorders, epilepsies, andmigraine; drugs for stopping drug additions and abuses;anti-inflammatory agents; drugs to treat hypertension, cardiovasculardiseases, gastric acidity and ulcers; drugs for hormone replacementtherapies and contraceptives such as estrogens and androgens;antibiotics, antifungals, antiviral and other antimicrobial agents;antineoplastic agents, immunosuppressive agents and immunostimulants;and drugs acting on blood and the blood forming argans includinghematopoietic agents and anticoagulants, thrombolytics, and antiplateletdrugs. Other active agents that can be delivered into the body using theshear device in the present invention include vaccines for variousdiseases, such as those for influenza, AIDS, hepatitis, measles, mumps,rubella, rabies, rubella, avercella, tetanus, hypogammaglobulinemia, Rhdisease, diphtheria, botulism, snakebite, back widow bite and otherinsect bite/sting, idiopathic thrombocytopenic purpura (ITP), chroniclymphocytic leukemia, cytomegalovirus (CMV) infection, acute renalrejection, oral polio, tuberculosis, pertussis, Haemophilus b,Pneumococcus, and Staphylococcus aureus.

In one embodiment, the carrier contains an anti-acne and/or anti-rosaceaagent. Examples of anti-acne and anti-rosacea agents include, but arenot limited to: retinoids such as tretinoin, isotretinoin, motretinide,adapalene, tazarotene, azelaic acid, and retinol; salicylic acid;benzoyl peroxide; resorcinol; sulfur; sulfacetamide; urea; antibioticssuch as tetracycline, clindamycin, metronidazole, and erythromycin;anti-inflammatory agents such as corticosteroids (e.g., hydrocortisone),ibuprofen, naproxen, and hetprofen; and imidazoles such as ketoconazoleand elubiol; and salts and prodrugs thereof. Other examples of anti-acneactive agents include essential oils, alpha-bisabolol, dipotassiumglycyrrhizinate, camphor, β-glucan, allantoin, feverfew, flavonoids suchas soy isoflavones, saw palmetto, chelating agents such as EDTA, lipaseinhibitors such as silver and copper ions, hydrolyzed vegetableproteins, inorganic ions of chloride, iodide, fluoride, and theirnonionic derivatives chlorine, iodine, fluorine, and other valences,synthetic phospholipids and natural phospholipids such as Arlasilk™phospholipids CDM, SV, EFA, PLN, and GLA (Uniqema, ICI Group ofCompanies, Wilton, UK).

In one embodiment, the device of the present invention contains ananti-aging agent. Examples of suitable anti-aging agents include, butare not limited to: inorganic sunscreens such as titanium dioxide andzinc oxide; organic sunscreens such as octyl-methoxy cinnamates;retinoids; dimethylaminoathanol (DMAE), copper containing peptides,vitamins such as vitamin E, vitamin A, vitamin C, and vitamin B andvitamin salts or derivatives such as ascorbic acid di-glucoside andvitamin E acetate or palmitate; alpha hydroxy acids and their precursorssuch as glycolic acid, citric acid, lactic acid, malic acid, mandelicacid, ascorbic acid, alpha-hydroxybutyric acid, alpha-hydroxyisobutyricacid, alpha-hydroxyisocaproic acid, atrrolactic acid,alpha-hydroxyisovaleric acid, ethyl pyruvate, galacturonic acid,glucoheptonic acid, glucoheptono 1,4-lactone, gluconic acid,gluconolactone, glucuronic acid, glucuronolactone, isopropyl pyruvate,methylpyruvate, mucic acid, pyruvic acid, saccharic acid, saccaric acid1,4-lactone, tartaric acid, and tartronic acid; beta hydroxy acids suchas beta-hydroxybutyric acid, beta-phenyl-lactic acid, andbeta-phenylpyruvic acid; zinc and zinc containing compounds such as zincoxides; and botanical extracts such as green tea, soy, milk thistle,algae, aloe, angelica, bitter orange, coffee, goldthread, grapefruit,hoellen, honeysuckle, Job's tears, lithospermum, mulberry, peony,puerarua, nice, and safflower; and salts and prodrugs thereof.

In one embodiment, the carrier contains a depigmentation agent. Examplesof suitable depigmentation agents include, but are not limited to: soyextract; soy isoflavones; retinoids such as retinol; kojic acid; kojicdipalmitate; hydroquinone; arbutin; transexamic acid; vitamins such asniacin and vitamin C; azelaic acid; linolenic acid and linoleic acid;placertia; licorice; and extracts such as chamomile and green tea; andsalts and prodrugs thereof.

In one embodiment, the carrier contains a plant extract. Examples ofplant extracts include, but are not limited to, feverfew, soy, glycinesoja, oatmeal, what, aloe vera, cranberry, hazel witch, alnus, arnica,artemisia capillaris, asiasarum root, birch, calendula, chamomile,cnidium, comfrey, fennel, galla rhois, hawthorn, houttuynia, hypericum,jujube, kiwi, licorice, magnolia, olive, peppermint, philodendron,salvia, sasa albo-marginata, natural isoflavonoids, soy isoflavones, andnatural essential oils.

In one embodiment, the carrier contains metals such as metal ions, metalsalts, metal complexes, fine metal powders, fine metal coated fibers andfabrics of synthetic or natural origin, or fine metal fibers. Examplesof such metals include, but are not limited to, zinc, copper, aluminum,gold, silver, titanium. The metal ions provide benefits such asantimicrobial, anti-inflammatory, and/or sebum-reduction effects. Thebeneficial metal ions may be released from the metal anode as the resultof an electrochemical oxidation reaction concurrent with electriccurrent passage (e.g., zinc ions electrochemically generated from a zincanode).

In another embodiment, the beneficial ions may be generated indirectlyfrom the electrochemical reactions at the electrode surface, such as thegeneration of hydrogen or hydroxyl ions at an inert electrode, whichsubsequently leads to a process to generate beneficial ions. Forexample, a device of the present invention may contain a power source,an inert anode (e.g., platinum, platinum coated conductive electrode,gold, or gold-coated conductive electrode), a reactive cathode (e.g.,silver/silver chloride electrode), and an aqueous carrier compositioncontaining an oxide (e.g., zinc oxide particles) among other activeagents. During application to the skin, the electrolysis of water at theinert anode produces excess hydrogen ions which acidify the carriertoward a lower pH value, while the electrochemical reaction at thereactive cathode (e.g., the conversion of silver chloride to silverions) does not affect the pH. As the solution becomes more acidic, theoxide starts to dissolve to release ions (e.g., zinc ions) for theirbeneficial effects to the barrier membrane.

Other active agents include those commonly used as for topical treatmentand in cosmetic treatment of skin tissues, such as topical antibioticsfor wounds, topical antifungal drugs to treat fungal infections of theskin and nails, and antipsoriatic drugs to treat psoriatic lesions ofthe skin and psoriatic nails.

Examples of antifungal drugs include but are not limited to miconazole,econazole, ketoconazole, sertaconazole, itraconazole, fluconazole,voriconazole, clioquinol, bifoconazole, terconazole, butoconazole,tioconazole, oxiconazole, sulconazole, saperconazole, clotrimazole,undecylenic acid, haloprogin, butenafine, tolnaftate, nystatin,ciclopirox olamine, terbinafine, amorolfine, naftifine, elubiol,griseofulvin, and their pharmaceutically acceptable salts and prodrugs.In one embodiment, the antifungal drugs are an azole, an allylamine, ora mixture thereof.

Examples of antibiotics (or antiseptics) include but are not limited tomupirocin, neomycin sulfate bacitracin, polymyxin B, 1-ofloxacin,tetracyclines (chlortetracycline hydrochloride, oxytetracycline-10hydrochloride and tetrachcycline hydrochoride), clindamycin phsphate,gentamicin sulfate, metronidazole, hexylresorcinol, methylbenzethoniumchloride, phenol, quaternary ammonium compounds, tea tree oil, and theirpharmaceutically acceptable salts and prodrugs.

Examples of antimicrobials include but are not limited to salts ofchlorhexidine, such as Iodopropynyl butylcarbamate, diazolidinyl urea,chlorhexidene digluconate, chlorhexidene acetate, chlorhexideneisethionate, and chlorhexidene hydrochloride. Other cationicantimicrobials may also be used, such as benzalkonium chloride,benzethonium chloride, triclocarbon, polyhexamethylene biguanide,cetylpyridium chloride, methyl and benzothonium chloride. Otherantimicrobials include, but are not limited to: halogenated phenoliccompounds, such as 2,4,4′,-trichloro-2-hydroxy diphenyl ether(Triclosan); parachlorometa xylenol (PCMX); and short chain alcohols,such as ethanol, propanol, and the like. In one embodiment, the alcoholis preferably at a low concentration (e.g., less than about 10% byweight of the carrier, such as less than 5% by weight of the carrier) sothat it does not cause undue drying of the barrier membrane.

Examples of antipsoriatic drugs or drugs for seborrheic dermatitistreatment include, but are not limited to, corticosteroids (e.g.,betamethasone dipropionate, betamethasone valerate, clobetasolpropionate, diflorasone diacetate, halobetasol propionate,triamcinonide, dexamethasone, fluocinonide, fluocinolone acetonide,halcinonide, triamcinolone acetate, hydrocortisone, hydrocortisonevenerate, hydrocortisone butyrate, aclometasone dipropionte,flurandrenolide, mometasone furoate, methylprednisolone acetate),methotrexate, cyclosporine, calcipotriene, anthraline, shale oil andderivatives thereof, elubiol, ketoconazole, coal tar, salicylic acid,zinc pyrithione, selenium sulfide, hydrocortisone, sulfur, menthol, andpramoxine hydrochloride, and salts and prodrugs thereof.

Examples of anti-viral agents for viral infections such as herpes andhepatitis, include, but are not limited to, imiquimod and itsderivatives, podofilox, podophyllin, interferon alpha, acyclovir,famcyclovir, valcyclovir, reticulos and cidofovir, and salts andprodrugs thereof.

Examples of anti-inflammatory agent, include, but are not limited to,suitable steroidal anti-inflammatory agents such as corticosteroids suchas hydrocortisone, hydroxyltriamcinolone alphamethyl dexamethasone,dexamethasone-phosphate, beclomethasone dipropionate, clobetasolvalerate, desonide, desoxymethasone, desoxycorticosterone acetate,dexamethasone, dichlorisone, diflorasone diacetate, diflucortolonevalerate, fluadrenolone, fluclarolone acetonide, fludrocortisone,flumethasone pivalate, fluosinolone acetonide, fluocinonide, flucortinebutylester, fluocortolone, fluprednidene (fluprednylidene)acetate,flurandrenolone, halcinonide, hydrocortisone acetate, hydrocortisonebutyrate, methylprednisolone, triamcinolone acetonide, cortisone,cortodoxone, flucetonide, fludrocortisone, difluorosone diacetate,fluradrenalone acetonide, medrysone, amciafel, amcinafide,betamethasone, chlorprednisone, chlorprednisone acetate, clocortelone,clescinolone, dichlorisone, difluprednate, flucloronide, flunisolide,fluoromethalone, fluperolone, fluprednisolone, hydrocortisone valerate,hydrocortisone cyclopentylproprionate, hydrocortamate, meprednisone,paramethasone, prednisolone, prednisone, beclomethasone dipropionate,betamethasone dipropionate, triamcinolone, and salts are prodrugsthereof. The preferred steroidal anti-inflammatory for use in thepresent invention is hydrocortisone. A second class of anti-inflammatoryagents which is useful in the compositions of the present inventionincludes the nonsteroidal anti-inflammatory agents.

Other active agents include, but are not limited to, wound healingenhancing agent, such as recombinant human platelet-derived growthfactor (PDGF) and other growth factors, ketanserin, iloprost,prostaglandin E₁ and hyaluronic acid, scar reducing agents such asmannose-6-phosphate, analgesic agents, anesthetics, hair growthenhancing agents such as minoxadil, hair growth retarding agents such aseflornithine hydrochloride, antihypertensives, drugs to treat coronaryartery diseases, anticancer agents, endocrine and metabolic medication,neurologic medications, medication for cessation of chemical additions,motion sickness, protein and peptide drugs.

In one embodiment, the carrier contains a fragrance effective forreducing stress, calming, and/or affecting sleep such as lavender andchamomile. The amount of the active agent in the carrier will depend onthe active agent and/or the intended use of the device. In oneembodiment, the carrier contains a safe and effective amount of theactive agent, for example, from about 0.001 percent to about 20 percent,by weight, such as from about 0.01 percent to about 5 percent, byweight, of the carrier.

Light Emitting Diode

In one embodiment, the device contains one or more light emittingdiodes. Light emitting diodes (LEDs) of certain spectrum may beincorporated into the device to emit light to the barrier membrane(e.g., to treat skin conditions such as acne and rosacea). The lightemitting diode may also provide a signal to the user indicating that thedevice is operating properly.

In one embodiment, the LED is one that emits light periodically (i.e., ablinking LED). In a further embodiment, such LED also modulates thecurrent passing through the barrier membrane to form a pulsatile DCcurrent. Such pulsatile DC current can enhance delivery of active agentsinto the barrier membrane, stimulate biological responses in the barriermembrane such as enhancing wound healing (e.g., in acne lesions), and/orenhanced skin sensation which serves a signal to a user that the deviceis working. Another potential advantage of using a blinking LED is toproduce pulsatile DC current without the need of a complex electriccircuit.

The spectrum of the LED's according to the current invention may rangefrom about 300 nm to about 1500 nm, such as from about 350 nm to about1000 nm. In one embodiment, the range of the LED includes violet-blue,green, red, and infrared ranges, e.g., from about 400 nm to about 450 nmsuch as from about 407 nm to about 420 nm; from about 510 nm to about550 nm; from about 600 nm to about 700 nm; and from about 1300 nm toabout 1500 nm. In one embodiment, the device contains two LEDs, one thatemits light having a wavelength of from about 400 nm to about 500 nm andone which emits light from about 700 nm to about 1000 nm.Photosensitizer agents, such as 5-aminolaevulinic acid (ALA), hypericin,St. John's wort powder or extract, or other synthetic or naturalphotosensitizer agents, may be incorporated into the carrier as activeagents to be delivered and irradiated by the device with LED's of thepresent invention. The light irradiation from the LED's, together withthe photosensitizer agent(s) and other aforementioned active agents,electrochemically generated oxidizing agents (e.g., peroxides, nascentoxygen, chlorine dioxide, and chlorine), and/or electric stimulation ofthe barrier membrane may work synergistically to achieve an improvedefficacy in treating membrane disorders such as acne and rosacea.

General Use

In one embodiment, the device is used for the treatment of a barriermembrane condition (e.g., the delivery of an active agent light, and/orelectricity into the membrane such as the skin, eye (cornea, retina,etc.), oral, buccal, nasal, vaginal, gastrointestinal, or rectal mucosabarrier membrane, of a human). In one embodiment, the device is used forthe treatment of skin conditions. Examples of such treatments include,but are not limited to: treatment of acne, rosacea, or other microbialinfections of the skin; reduction the visible signs of skin aging (e.g.,wrinkles, sagging, and age-spots); folliculitis and pseudo-folliculitisbarbae; treatment of wounds and lesions (e.g., enhancing healing andscar reduction); sebum regulations (e.g., sebum reduction oroily/shining skin appearance inhibition or control); pigmentationregulation (e.g., reduction of hyperpigmentation or pigmentation oflight skin); hair growth retardation (e.g., skin on the leg) or hairstimulation (e.g., scalp); and treatment of dermatitis (e.g., atopic,contact, or seborrheic dermatitis) and/or psoriasis.

In another embodiment, the device is used for the treatment of mucosalconditions (e.g., mucosa in the oral or vaginal cavities). Examples ofsuch treatments include, but are not limited to: treatment of vaginalcandidiasis and vaginosis, genital and oral herpes, cold sore, cankersore, oral hygiene, periodontal disease, and other microbial infectionsof the mucosa.

Another embodiment of the present invention is the device inducescertain desirable biological responses that facilitate the treatment ofthe barrier membrane conditions. These desirable biological responsesmay be induced by the electric current passage through the barriermembrane, and/or the electrochemically generated oxidizing materials,together with the active agents delivered by iontophoresis from thecarrier, in treating the barrier conditions. Examples of the desirableresponses of the barrier membrane may include, but are not limited to,sebum regulation (e.g., reduction of sebaceous gland activity),inhibition of anaerobotic microbial growth and establishment of ahealthier membrane microflora or (e.g, reduction of P. acne growth andof production of irritating fatty acids), blood vasoconstriction (thuspromoting local accumulation of active agents or removal of dark circleunder the eye due to deoxyhemoglobins), enhanced tissue immunologicalactivity (e.g, increased elimination of pathogenic microbes on tissue'sown defense systems), improved tissue repairing (e.g., enhanced healingand reduced scarring of lesions such as acne lesions), and improvedkeratolytic activity of the carrier (e.g., softening of keratin plugs ofcomedos in whiteheads and blackheads of acne, and facilitating theirremoval).

In another aspect, the invention also features the method of convertingan active agent from a less active form to a more active form viaoxidation or reduction via an inert electrode (e.g., cystine tocysteine, disulfide acetyl-cysteine to acetyl-cysteine, and retinol toretinoic acid). Thus, an unstable agent can be stored in a more stableform and converted to its active form prior to administration. In afurther aspect, the generation of reducing agents by the device of thepresent invention can be used to stabilize oxygen-labile active agents.Examples of such oxygen-labile active agents include, but are notlimited to, retinoids, ascorbic acid, and benzoyl peroxide.

In one embodiment, the invention also features the method of convertingan active agent from a less active form to a more active form viaoxidation at an reactive anode, such as an anode made of zinc,magnesium, copper, aluminum, alloy or mixture of these metals. Forexample, an anode made of zinc releases zinc ions with the passage of anelectric current through the electrode. The zinc ions generated by suchan electrochemical reactions are then subsequently delivered by theelectric repulsion of the positively charged anode into the barriermembrane. In one embodiment, such ions are deposited into the hairfollicles and/or sebaceous glands to inhibit P. acnesgrowth and/orsuppress skin tissue inflammation resulted from P. acnes over growthbefore the treatment. Similarly, a zinc-copper alloy anode or anotherzinc-beneficial metal alloy releases both zinc ions and copper ions orthe other beneficial ions, respecytively, into the hair follicles andsebaceous glands for acne treatment and prevention.

Skin Conditions

In one embodiment, the device of the present invention is used to treatskin conditions such as: acne and acne (e.g., blackheads and whiteheads)and acne-related skin conditions such as rosacea and nodule-cystic;hyperpigmentation such as freckles, melasma, actinic and senilelentigines, age-spots, post-inflammatory hypermelanosis, Becker'snaevus, dark circles under the eye, and facial melanosis; stretch marks;and skin aging effects on the skin (such as those caused by photodamage)including wrinkling, roughness, pigmentary alterations, sallowness, finelines, and laxity, by delivering active agents that includingpre-formulated active agents in the carrier and electrochemicallygenerated active agents (e.g., beneficial metal ions) by the electrodes,and/or by providing electric stimulation to the skin tissues.

In one embodiment, the device of the present invention provide multiplemechanism of actions to treat such conditions: namely, (a)target-delivering pre-formulated active agents into the pilosebaceousunit by iontophoresis and electro-osmosis; (b) electrochemicallygenerating new active agents (e.g., the beneficial metal ions from areactive anode) and targeted delivery of the freshly generated activeagents to the pilosebaceous unit (e.g., beneficial ions such as zinc andcopper have known to enhance skin's own immune system); and/or (c)providing electric stimulation to the pilosebaceous unit and itssurrounding skin tissues to increase blood circulation, and to treat theskin by reducing inflammation, enhancing wound healing, and/orincreasing skin exfoliation.

Wounds and Scars

In one embodiment, the device of the present invention can beincorporated into wound dressings and bandages to provide electrictherapy for healing enhancement and scar prenvetion. In one embodiment,the wound exudation fluid and/or wound cleansing solution serves toactivate a galvanic wound dressing/bandage to deliver active agentspre-incorporated in the wound dressing/bandage and/or to generateelectrochemically beneficial metal ions followed with delivery of thebeneficial metal ions into the wound. The device also treats the woundwith therapeutic electric current which may increase blood circulation,stimulate tissue immune response, and/or suppress tissue inflammation,which may lead to accelerated healing and reduced scarring.

Enhanced Chemical Peel

Chemical peel treatments are an in-office procedure that involves theapplication of a chemical agent to the skin to induce controlleddestruction or exfoliation of old skin and stimulation of new epidermalgrowth with more evenly distributed melanin. When peel agents reach thedermal layer, important wound-healing activities occur that cause skinremodeling and skin smoothing, both are anti-aging benefits. Delivery ofchemical peel agents contained with the carrier of electrical generatingdevice/composition could be used in the treatments for a variety of skindisorders, including but not limiting to, acne, post-inflammatoryhyperpigmentation, melasma, scar, photo-damage, age-spot, wrinkle,stretch mark, birth mark, uneven texture and tone, warts, andpseudofolliculitis barbae. The device/composition may also have theadditional advantage of reducing skin irritation and decreasing the riskof precancerous and early cancerous lesions of the photo-aged skin onthe face, because the iontophoretically administrated chemical peel mayenable the use of a much lower concentration of chemical peeling agentsin comparison to the standard chemical peel approach without the use ofsuch device. Reduction of required chemical peeling agents may alsominimize risk of prolonged post-peel erythema, inflammation and scarsfrom chemical peel while achieving desirable benefits.

Examples of chemical peel agents include, but are not limited to: hydoxyacids such as α-hydroxy acids such as lactic acid, malic acid, glycolicacid, arginine glycolate, ammonium glycolate and sodium glycolate;β-hydroxy acids such as salicylic acid; polyhydroxy acids (PHA) such asgluconolactone; and non-hydroxy acids such as acetic acid,trichloroacetic acid (TCA), pyruvic acid an alpha-keto-acid, phenol,their derivatives or their combinations. They can also be combined withsulfur, resorcinol, retinoids or other active actives such as Jessnersolution peel (which contains lactic acid, salicylic acid, resorcinoland ethyl alcohol). Chemical peeling agents of the present invention mayalso include, but are not limited, protease agents or their derivativessuch as acid protease in the apoenzyme, holoenzyme, idoenzyme, orzymogen form. Examples include pepsin, Bromelain, papaya, and cathepsin.Further examples include natural extract chemical peeling agents such asfruit extracts, mushroom extract, and other plant extracts.

In one embodiment, the duration of the application of the device to theskin is from about 2 to about 10 minutes depending on the individualskin conditions. In one embodiment, the carrier contains from about 0.1%to about 70% by weight of such chemical peel agent, such as from about0.5% to about 20% such as from about 2% to about 10%.

Shape

The device includes a housing that may be fabricated into various shapesand sizes to fit the contours of various anatomical surfaces of thebarrier membranes. For examples, the housing may be a substrate made inthe shape of a whole facial mask with openings/holes to expose the eyes,eye bows, nose, and mouth; a partial facial mask covering only the upperor lower half of the face; or a patch covering only the forehead, or theunder eye region, the chin and jaw region, the neck, the back, wound,acne lesion or pimple, or other specific area of a barrier membrane inneed of treatment.

In one embodiment of the present invention, the housing is awater-insoluble substrate containing a galvanic couple, for example, afine zinc wire or a fine zinc-coated fiber (e.g., zinc-coated polymerfiber) connected to a fine copper wire or a fine copper-coated fiber(e.g., copper-coated polymer fiber). One or more such fine galvaniccouple wire(s) or fiber(s) may be incorporated into the substrate tocreate a device which, when in contact with the carrier (such as tapwater or a liquid or semi-liquid composition including active agents)generates an electric current. In one embodiment, a galvaniccouple-containing substrate may be made of multiple layer, for example,a layer of the zinc-containing substrate (e.g., a fine zinc wire- or afine zinc-coated fiber in a woven or non-woven fabric) over a layer ofcopper-containing substrate (e.g., a fine copper wire- or a finecopper-coated fiber in a woven or non-woven fabric). During use, thelayers contact each other to form the galvanic couple. In a furtherembodiment, the device releases beneficial ions (e.g., zinc ions oraluminum ions) that are delivered to the barrier membrane (e.g., theskin) when such a substrate is applied by the user (e.g., used as a wipefor cleaning the skin or a facial patch or mask to treat the skin).Active agents may also be incorporated into the substrate duringmanufacturing processes or be subsequently applied to the substarteprior to the application to the barrier membrane (e.g., in the form ofan electrolyte or active agent containing liquid spray to wet thesubstrate). In one embodiment, the fabric is used as a dry wipe or a dryfull or partial facial mask, to be wetted immediately before use, byapplying water to the dry wipe or facial mask to pre-moisturized skin(e.g., by washing with tap water).

By “water insoluble” is meant that the substrate, upon immersion indistilled water at 25° C., does not readily dissolve in or readily breakapart. The water-insoluble substrate may, however, be disintegratedand/or dissolved slowly, i.e., over a period of several hours up toseveral days. A wide variety of materials can be used as thewater-insoluble substrate. Examples of suitable substrates include, butare not limited to, non-woven substrates, woven substrates,hydro-entangled substrates, air entangled substrates, natural sponges,synthetic sponges, and polymeric netted meshes.

The water insoluble substrates may be flushable. As used herein, by“flushable” is meant that the substrate will pass through at least 10feet of waste pipe in two toilet flushes. The material may also bebiodegradable.

In one embodiment, the substrates contain a non-woven material. By“non-woven” is meant that the substrate, or a layer of the substrate, iscomprised of fibers that are not woven into a fabric but rather areformed into a sheet, mat, or pad layer. The fibers can either be random(i.e., randomly aligned) or they can be carded (i.e., combed to beoriented in primarily one direction. Furthermore, the non-wovensubstrate can be composed of a combination of layers of random andcarded fibers).

Non-woven substrates may be comprised of a variety of natural and/orsynthetic materials. By “natural” is meant that the materials arederived from plants, animals, insects, or byproducts of plants, animals,and insects. By “synthetic” is meant that the materials are obtainedprimarily from various man-made materials or from natural materials,which have been further altered. Non-limiting examples of naturalmaterials useful in the present invention are silk fibers, keratinfibers (such as wool fibers, camel hair fibers) and cellulosic fibers(such as wood pulp fibers, cotton fibers, hemp fibers, jute fibers, andflax fibers).

Examples of synthetic materials include, but are not limited to, thoseselected from the group containing acetate fibers, acrylic fibers,cellulose ester fibers, cotton fibers, modacrylic fibers, polyamidefibers, polyester fibers, polyolefin fibers, polyvinyl alcohol fibers,rayon fibers, polyurethane foam, and mixtures thereof.

Substrates made from one ore more of the natural and synthetic materialsuseful in the present invention can be obtained from a wide variety ofcommercial sources such as Freudenberg & Co. (Durham, N.C. USA), BBANonwovens (Nashville, Tenn. USA), PGI Nonwovens (North Charleston, S.C.USA), Buckeye Technologies/Walkisoft (Memphis, Tenn. USA), and FortJames Corporation (Deerfield, Ill. USA).

Methods of making non-woven substrates are also well known in the art.Such methods include, but are not limited to, air-laying, water-laying,melt-blowing, spin-bonding, or carding processes. The resultingsubstrate, regardless of its method of production or composition, isthen subjected to at least one of several types of bonding operations toanchor the individual fibers together to form a self-sustaining web. Thenon-woven substrate can be prepared by a variety of processes includinghydro-entanglement, thermally bonding, and combinations of theseprocesses. Moreover, the substrates can have a single layer or multiplelayers. In addition, a multi-layered substrate can include film layer(s)(e.g., aperture or non-aperture film layers) and other non-fibrousmaterials.

Strength or firmness of the non-woven material may be a desirableattribute. This can be achieved, for example, by the addition of bindingmaterials, such as wet strength resins, or the material may be made ofpolymer binder coatings, stable fibres, e.g. based on cotton, wool,linen and the like. Examples of wet strength resins include, but are notlimited to, vinyl acetate-ethylene (VAE) and ethylene-vinyl chloride(EVCL) Airflex emulsions (Air Products, Lehigh, Pa.), Flexbond acrylicpolymers (Air Products, Lehigh, Pa.), Rhoplex ST-954 acrylic binder(Rohm and Haas, Philadelphia, Pa.), and Ethylene-vinyl acetate (EVA)emulsion (DUR-O-SET® by National Starch Chemicals, Bridgewater, N.J.).The amount of binding material in the substrate may range from about 5%to about 20%, by weight, of the substrate.

Non-woven materials of increased strength can also be obtained by usingthe so-called spunlace or hydro-entanglement technique. In thistechnique, the individual fibers are twisted together so that anacceptable strength or firmness is obtained without the need to usebinding materials. The advantage of the latter technique is theexcellent softness of the non-woven material.

In one embodiment, the non-woven material is made of a superabsorbentpolymer. For the purposes of the present invention, the term“superabsorbent polymer” refers to materials which are capable ofabsorbing and retaining at least about 10 times their weight in bodyfluids under a 0.5 psi pressure. The superabsorbent polymer particles ofthe invention may be inorganic or organic crosslinked hydrophilicpolymers, such as polyvinyl alcohols, polyethylene oxides, crosslinkedstarches, guar gum, xanthan gum, and other material known to the art ofabsorbent article manufacture.

Additives may also be added in order to increase the softness of thesubstrates. Examples of such additives include, but are not limited to,polyols such as glycerol, propylene glycol and polyethylene glycol,phthalate derivatives, citric esters, surfactants such aspolyoxyethylene (20) sorbitan esters, and acetylated monoglycerides.

Sensory attributes may also be incorporated to the insoluble non-wovensubstrates. Examples of such sensory attributes include, but are notlimited to color, texture, pattern, and embossing.

In one embodiment, the device of the present invention is for use as awipe or towel (for example, having a surface area of from about 20 cm²to about 10,000 cm²). In another embodiment, the device of the presentinvention is for use as a therapeutic patch or mask for application to aportion of or substantially all of the face (for example, having asurface area of from about 1 cm² to about 600 cm²)

In one embodiment, the carrier is present in at least about 50%, such asat least about 75%, by weight of the total weight of the water insolublesubstrate prior to use. In another embodiment, (i) the liquid carrier ispresent in less than about 10%, such as less than about 1%, by weight ofthe total weight of the water insoluble substrate (for example, thedevice may not contain any carrier prior to use). In a furtherembodiment, the product contains instructions for the user to either (i)wet the substrate prior to application or (ii) wet the barrier membrane(e.g., the skin) with water and/or another liquid prior to application.

Devices

One embodiment of the present invention is represented schematically inFIG. 1. The device 500 contains a removable release liner 100, a carrierlayer 120, a first conductive electrode 140, a second conductiveelectrode 240, electric lead wires 110 and 210 connecting the two endsof an electrically insulated connecting wire 350 to the two dissimilarconductive electrodes, an optional electric power switch 330 located onthe lead wire 210, a backing layer 160, and a cover layer 340.

The gap “b” depicts the distance between two conductive electrodes 140and 240 to the release liner (or the membrane following application ofthe device), and the gap “a” represents the distance between twooppositely charged conductive electrodes. In one embodiment, gap “a” isbetween 0 to about 20 centimeter, and gap “b” is between 0 and to about1 centimeters. In another embodiment, the ratio of gap “a” to gap “b” isfrom about 0 to about 20.

The backing layer 160 may be impermeable to the active agent containedwithin the carrier layer 120, and is preferably not permeable to wateror other solvents in the carrier layer 120. The backing layer 160 andcover layer 340 may be made of flexible material that is impermeable towater and electrically insulating, e.g., polymers such as polyethylene,polypropylene, polyvinyl acetate, polyurethane, silicone rubber, orpolyvinyl chloride.

In a further embodiment, the backing layer 160 is permeable toelectrochemically generated gases (e.g., oxygen, chlorine, and hydrogen)in order to limit excess accumulation of the gases in the carrier whichcan cause tissue irritation and/or undesirable deformation of thedevice. Examples of such “breathable backing” material include, but arenot limited to, a cotton or synthetic woven and nonwoven fabric layer,such as those fabric materials commonly used for bandages and sportsbandages.

The carrier layer 120 is an adhesive hydrogel containing the activeagent. The active agent may be incorporated into the carrier layer 120as dissolved molecules and ions, dispersed solid particles, or liquiddroplets such as cream, lotion, emulsion, multi-emulsion, microemulsion,and/or liposome compositions. The carrier layer 120 may also contain asolid supporting matrix (e.g., a gauze, non-woven or sponge-likematerial).

A removable liner sheet 100 covers the carrier layer 120. The selectionof the removable release-liner 100 is dependent on the type of theadhesive hydrogel used in carrier layer 120. The release liner sheet 100is typically a polymer sheet or a paper or fabric coated with a polymer,which has weak adhesion toward the adhesive hydrogel layer 120, therebyallowing it to be easily removed from the carrier layer 120 prior to usewithout damaging the carrier layer 120. Examples of the polymerstypically used for the release liner 100 are silicones andpolyethylenes. Alternatively, a wax may be used in the place of thepolymer to coat the release liner 100.

In addition to, or in lieu of, the use of an adhesive in the carrierlayer 120, the device 500 may be fastened to the barrier membrane withan adhesive tape, an elastic band, a band with a buckle (similar to aleather watch band), or a Velcro® band.

In order to use device 500, the removable release liner sheet 100 ispeeled off, and the carrier hydrogel layer 120 of the device 500 isaffixed to a barrier membrane, such as the skin or mucosal membranessuch as vaginal, oral, buccal, nasal, gastrointestinal or rectal mucosabarrier membrane, of the user. The device may be directly affixed to thebarrier membrane if the carrier layer 120 contains an adhesive hydrogel.An electric potential is applied across the conductive electrodes 140and 240 by switching on the power switch 330.

Another embodiment of the present invention is represented schematicallyin FIG. 2. The electrically insulated connecting wire 350 is locatedwithin the carrier layer 120. The advantage of this arrangement includesreduced bulkiness, enhanced esthetics and user comfort.

The lighting portion of the LED 122 is preferable located in the carrierlayer 120 in close proximity to the skin. Locating the light source inthe carrier layer 120 affixed to the barrier membrane has an advantageof minimizing the loss of light energy from reflection of skin surface.In addition, a light reflective layer may be used as the backing layer160 (e.g., metalized polymer film) to further enhance the efficacy ofphototherapy, and to achieve more homogeneous irradiation. The backinglayer 160 may optionally be perforated as certain spots to make thelight visible to the user to serve as an indicator that the device isworking normally.

Another embodiment of the present invention is represented schematicallyin FIG. 3. Backing layer 160 (e.g., the housing) contains an adhesivelayer 130 coated onto the outer rim of the backing layer 160 foraffixing device 500 to membrane during application. The adhesive in theadhesive layer 130 may be a polymeric, pressure sensitive and/ornonconductive. Suitable adhesive materials include, but are not limitedto, silicones, polyisobutylenes and derivatives thereof, acrylics,natural rubbers, and combinations thereof. Suitable silicone adhesivesinclude, but are not limited to, Dow Corning 355 (available from DowCorning of Midland, Mich.); Dow Corning X7-2920; Dow Corning 0 X7-2960;GE 6574 (available from General Electric Company of Waterford, N.Y.);and silicone pressure sensitive adhesives. Suitable acrylic adhesivesinclude, but are not limited to, vinyl acetate-acrylate multipolymers,including, such as Gelva-7371 (available from Monsanto Company of St.Louis, Mo.); Gelva T 7881; Gelvac 2943; 1-780 medical grade adhesiveavailable from Avery Dennison of Painesville, Ohio; and acrylic pressuresensitive adhesives.

One embodiment of the present invention is a dual-pack system, in whichthe galvanic device and the carrier (or a portion of the carrier) arepackaged separately. One portion of the carrier layer 120 may be ananhydrous liquid-immobilizing matrix, such as a dry woven or nonwovenfabric, a sponge, or a dehydrated hydrogel layer (e.g., freez-driedhydrogel), while the liquid portion of the carrier, such as a solution,gel, or cream containing active agents, is packaged in a separate liquidcontaining compartment (not shown in the figures), such as a unit dosepouch, a breakable container or a bottle. Prior to use, theliquid-containing compartment is broken and the liquid or semisolidportion of the carrier is applied to the liquid-immobilizing matrix toactivate the galvanic current generation for skin application. Theactive agents are either incorporated into the liquid-immobilizingmatrix or the liquid/semisolid composition.

One embodiment of the present invention is represented schematically inFIG. 4. The conductive electrodes 140 and 240 is in electriccommunication with each other through direct connection, namely, the gap“a” (the distance between two oppositely charged conductive electrodes)is equal to zero. Two conductive electrodes forms a galvanic couplewhich is contact the carrier layer 120 enclosed in backing layer 160with an opening affixed to the release liner 100 with an adhesive layer130. One major advantage of this configuration is its simplicity andeasiness to manufacture.

Another embodiment of the present invention is represented schematicallyin FIG. 5. The electrotransport device 800 containes two electrodeassemblies 200 and 600, respective adhesive layers 230 and 630,respective carrier layers 220 and 620, respective conductive electrodes240 and 640, respective backing layers 270 and 670, respective electricleads 210 and 610, electrically insulated connecting wire 350 andoptional electric switch 330. Similar to the aforementioned typicaliontophoresis device, the two electrode assemblies 200 and 600 are to beaffixed to the barrier membrane apart from each other, after the releaseliner 100 is removed prior to use.

In one embodiment, the carrier layer 120 contains at least two activeagents carrying opposite electric charges. One example of such acomposition is a composition containing from about 0.5 to about 2% ofsalicylic acid and from about 0.01 to about 0.2% of a cationicquaternary ammonium antimicrobial agents (such as benzalkonium chloride,benzethonium chloride, methyl benzethonium chloride, and cetylpyridiniumchloride), phenol, and/or chlorhexidine gluconate. The device 500 of thepresent invention can simultaneously deliver both active agents ofopposite charges into the membrane.

FIGS. 6 and 7 show two examples of different configurations ofdissimilar conductive electrodes 140 (shown by a double line) and 240(shown by a single line) in carrier layer 120, connected by electricallyinsulated wires 350 (shown by a triple line) to form a galvanic couplepower source. FIG. 6 shows that the conductive electrodes 140 and 240are arranged in an inter-digitated configuration. FIG. 7 shows theconductive electrodes in a concentric configuration.

FIGS. 8 and 9 show two examples of other configurations of dissimilarconductive electrodes 140 and 240 in carrier layer 120, connected toeach other either connective wire 350 as in FIG. 8 or by a directphysical contact at each intersection 370 as in FIG. 9 to form a pluralof galvanic couple power sources, which are in contact with the carrierlayer 120. The conductive electrodes 140 and 240 in FIGS. 8 and 9 arearranged in parallel and perpendicular configurations, respectively.

The alternating-parallel arrangement of the conductive electrodes 140and 240 in FIG. 8 provides a more uniform electric current distributionthroughout the carrier layer 120 and the underlying skin tissue, andconsequently, assist in enabling a more uniform delivery of activeagents into the skin. One exemplifying fabrication method for thegalvanic device shown in FIG. 8 is by weaving a silver-coated polymerfabric and zinc-coated polymer fabric (or zinc wire) into aliquid-absorbant fabric layer according to the parallel electrodepattern, then connecting zinc and silver electrodes by printing over thesilver and zinc regions with an electric conductive ink (e.g.,conductive silver or carbon ink). Covering another layer of an electricinsulating ink over the electric conductive ink will produce theelectrically insulated connecting wire 350.

Another fabrication method for the device of FIG. 8 is via printing: toprint onto a non-conductive polymeric substrate layer (e.g., the polymermaterial made of the backing layer 160) using a conductive silver orsilver-silver chloride ink to produce the first conductive electrode;and to print the second conductive electrode using a conductive zincink. The two dissimilar conductive electrodes are then connected byprinting cross them with either the conductive silver or zinc ink (or adifferent conductive ink such as carbon ink). A covering ink may thenoptionally be printed over the connecting wire to produce an electricinsulating polymer layer over it. If the device is made withoutinsulating with an electrically insulating coverying layer, theresulting device is a variation of that depicted in FIG. 9.

FIG. 9 is a top view of one embodiment in accordance with the inventionshowing the conductive electrodes 140 and 240 connected to each other bydirect physical contact at the intersections 370 to form a galvaniccouple power source, which is in contact with the carrier layer 120. Theconductive electrodes 140 and 240 are arranged in a perpendicularconfiguration. The aforementioned fabrication methods for the device inFIG. 8 is also suitable to produce this device.

FIG. 10 is a top view of one embodiment in accordance with the inventionshowing a device made of a zinc mesh having conductive-electrodes 140(shown in bold lines) and electrodes 240 (shown in double lines)connected by electrically insulated connecting wires 350 (shown insingle lines) embedded in the carrier layer 120. The conductiveelectrodes 140 are uncoated regions of the zinc mesh. The conductiveelectrodes 240 is prepared by coating the designated portion of the zincmesh with a silver-silver chloride ink. The electrically insulatedconnecting wire 350 is prepared by coating the designated portion of thezinc mesh with an electrically insulating paint, ink, or polymersolution.

FIG. 11 is a top view of one embodiment in accordance with the inventionshowing the conductive electrodes 140 and 240 embedded in the carrierlayer 120. The conductive electrodes 140 are made of a piece of zincmesh. The conductive electrodes 240 are prepared by coating thedesignated portion of the zinc mesh with a silver-silver chloride orsilver ink, or by other silver depositing methods such as electrolessdeposition (chemical reduction deposition), electroplating, plasmaspray, or vacuum deposition. Elimination of the electrically insulatedconnecting wire 350 in this design would simplify the manufacturingprocess. The location, pattern, shape, and size of the electrode ofmetallic silver, silver-silver chloride or silver-silver oxide may varydepending on the need of a particular products.

Zinc mesh (or “expanded zinc” as common called in battery andanti-corrosion fields) may be prepared from a thin zinc foil withmechanical perforation and subsequent expansion into net-like patterns.The major advantages of a zinc mesh anode in the galvanic device of thepresent invention are its ability of forming and retaining the desirablemask/patch shape by a user, stretching by a user toward any directionsto form mask/patch of desirable size; and being breathable.

It should be noted although the use of zinc mesh is described here as anexample of electrode designs, other aforementioned materials suitablefor galvanic couple formation and for conductive electrodes can also bemade into a mesh or an expanded form to provide the same function.

Zinc mesh also has the ability to conform to the shape of the membranesurface (e.g., the shape of an individual's face) by gently pressuringit, and to retain this shape. This capability makes it uniquely suitablefor a facial mask or certain skin patches to better fit the contours ofcertain anatomic features of the face (e.g., a nose patch) or bodyareas. This unique feature also assists in better electric contact andmay also reduce dependence on using adhesives to affix the device to theskin.

It is also highly convenient and desirable to a consumer if a facialmask or patch can be stretched to different sizes in order to cover aparticular skin area without compromising its electric performance. Azinc mesh anode (or other mesh conductive electrode) is uniquely capableto fulfill this consumer need. In another embodiment, the mesh is notexpanded before use so that the device is smaller and more compact foreasy storage and carrying. Rather, it is stretched open to a desiredsize during application by a consumer.

Good breathability is important for a facial mask or a patch ofrelatively large size, especially if the device is designed to be wornby a user for an extended period of time (e.g., longer than one halfhour such as overnight). In order to make aforementioned devicestretchable and/or breathable, the carrier layer 120 and backing layer160 should also be stretchable and breathable, such as stretchable wovenand nonwoven fabric materials.

In another embodiment, the backing layer 160 in FIGS. 3–5, can beperforated or eliminated entirely for a mask or patch device, which isespecially suitable for the application of short duration, e.g., fromabout 5 to about 30 minutes. As water in the carrier compositionevaporates, the electric conductance and the electric current decrease.Eventually, the electric current will significantly diminish, providingin essence a self-terminating device to serve as a safety measure forthe user to prevent any unintentional over-exposure of the skin to theelectric current and potential resulting skin damage.

One example of such a self-terminating device is a galvanic cloth facialmask made with a zinc mesh partially coated with silver-silver chlorideink, which is placed in between a backing film/housing (e.g., aperforated or nonperforated polyethylene film) and a nonwoven fabric(e.g., a polyester and/or rayon nonwoven sheet) using a binding processbased on heating, ultrasound or other mechanism. Prior to application, aliquid or semisolid carrier composition containing ionic and non-ioncactive agents and other optional electrolytes is applied to the nonwovenside of the device to activate the galvanic power source. The galvanicdevice is then pressed onto the user's face with the nonwoven side indirect contact with the skin. Alternatively, the active agents and otheroptional electrolyte may be incorporated in nonwoven layer duringmanufacturing process in an anhydrous state. In use, the device can beapplied to water-wetted face, and the water will dissolve the activeagents and electrolytes to activate the galvanic current. The anhydrousactive agents may be in the form of dry powder immobilized onto thefibers of the nonwoven, or dissolved first in an organic solvent (e.g.,polyethylene glycol, propylene glycol, glycerin, and/or alcohol) to forma non-conductive or very low conductive solution, which is absorbed inthe nonwoven layer.

The zinc anode materials may be manufactured with a wide variety ofmanufacturing process, including, but not limited to, metal processing,electroless deposition, electroplating, plasma spray, vacuum deposition,print processes such as screen printing using a zinc conductive ink,textile or nonwoven technologies. Similarly, other conductive metalmaterials, such as silver-silver chloride, silver-silver oxide, copper,magnesium, aluminum alloys of zinc, magnesium, copper and aluminum, maybe manufactured into the aforementioned electrode forms using themanufacturing processes disclosed above.

Topical Compositions Containing Galvanic Pairs

In one embodiment, the present invention features a topical compositioncontaining a first conductive metal particulates (such as fine flakes,wires/fibers or metal-coated fibers) selected from zinc, aluminum,copper, and their alloys; and a second conductive metal particulates(such as fine flakes, wires/fibers or metal-coated fibers) selected fromsilver, copper, gold, and their alloys. The first and second metalparticulates can be selected from aforementioned electrode materials toform galvanic couples. Upon contact, the first conductive metal and thesecond conductive metal form a galvanic pair, generates electriccurrent, and electrochemically generates ions. In a further embodiment,the difference of the standard potentials of the first conductive metaland the second conductive metal is at least about 0.1 V, such as atleast about 0.5 V. For example, upon contact with a first conductivemetal that contains zinc (such as fine zinc wires, zinc flakes orpolymer fibers coated with zinc) and a second conductive metal thatcontains silver (such as a fine silver wires/fibers, silver flakes, orpolymer fibers coated with silver), the composition generates electriccurrent and zinc ions within the topical composition.

The composition may additionally contain an active agent, such as ananti-acne agent (such as salicylic acid, benzoyl peroxide, retinoic acidand/or retinol). The topical composition containing the first metal andthe second metal is preferably a semi-solid dosage form (such as a gel,a hydrogel, a water-in-oil emulsion, an oil-in-water emulsion, a cream,a lotion, an ointment, a multi-emulsion, a liposome, and/or amicrocapsule formulation), and may contain the aforementioned fluidsuspending or fluid absorbing materials. The topical composition may beprepared as such that one of the conductive metal is formulated in aseparate phase from other conductive metal, for example, the firstconductive metal (e.g., zinc flakes) is formulated in the discontinuousoil phase of an oil-in-water emulsion (e.g., a cream), while the secondconductive metal (e.g., silver flakes) is formulated in the continuousaqueous phase of the emulsion. The topical composition of the presentinvention may also further contain a humectant (such as glycerin,propylene glycol, polyethylene glycol, sorbitol and/or urea) andaforementioned electrolytes to maintain certain moisture level andconductivity of the skin.

In one embodiment, during storage of such a topical composition, thefirst conductive metal and the second conduct metal are suspendedsubstantially apart in a semi-solid composition (e.g., are not incontact with each other). Upon application to the membrane (such as theskin or mucosa) and partial drying of the liquid carrier, the contact ofthe first conductive metal and the second conductive metals results ingalvanic couple formation and generation of electric current and metalions of the first conductive metal, which provides benefits to themembrane such as antimicrobial, anti-inflammation, wound healing,iontophoretic delivery of active agents, tissue stimulation, and/orsebum reduction.

In one embodiment, the wires/fibers, flakes of conductive metals, orpolymer fibers coated with the conductive metals are fine enough thatthey can be suspended in the semi-solid compositions during storage. Ina further embodiment, they are in elongated shapes. The advantages ofelongated shapes of the conductive metals (e.g., fine wires/fibers,flakes and polymer fibers coated with the conductive metals) include alower apparent density and, therefore, a better floating/suspendingcapability in the topical composition; a higher probability of connectedwith each other when low concentrations of the conductive metals areused; and a wider and deeper range of the membrane tissue (e.g., theskin) that the galvanic current travels through and provides thebenefits to.

In one embodiment, the first and second conductive metal particles areformulated into different compositions and are stored in separatecompartments of a dual chamber dispensing package. For example, the lesschemically stable (e.g., more oxidizable) zinc or its alloy particulatesmay be formulated in an anhydrous, essentially non-conductivecomposition with organic solvents such as polyethylene glycols,propylene glycol, glycerin, liquid silione and/or alcohol, or otherpharmaceutically-acceptable organic solvents. The more chemically stable(e.g., less oxidizable) silver and silver chloride particulates may beformulated in an aqueous composition. The active agents may beformulated into either composition depending on their chemical stabilityand solubility. In use, the compositions are dispensed from dual chamberpackage (e.g., dual chamber pump, tube, pouch, bottle, etc.) and mixedprior or during application to the skin to form galvanic couples in situto generate galvanic current and to treat the skin conditions.

In another embodiment, the aforementioned galvanic couples aremanufactured as particulates to be incorporated into topicalcompositions. The particulates may be of any shape, including but notlimited to, spherical or non-spherical particles or elongated orflattened shapes (e.g., metal or metal-coated spheres, hollow metal ormetal-coated spheres, short metal-coated fibers or fabrics, and flakes),regular shapes (e.g., metal crystals), and irregular shapes (e.g.,aggregated spheres). In one embodiment, the particulates have an averageparticle size of from about 1 micrometer to about 2 centimeters. What ismeant by the particle size the maximum dimension in at least onedirection. In one embodiment, the particulates have an average particlesize of from about 1 micrometer to about 2 millimeters for non-elongatedshapes. In another embodiment, the particulates with elongated shapeshave an average particle size from about 10 micrometers to about 2centimeters such as from about 100 micrometers to about 50 millimeters.For example, a polymer fiber of about 100 micrometers to about 10millimeters in length may be coated partially with silver orsilver-silver chloride on one end (or only on certain portions of thefiber), and zinc on the other end (or on the remaining portions). Inanother example, the polymer fiber is coated completely with the firstconductive metal (e.g., silver-silver oxide or silver-silver chloride),and one end (or certain portions of the fiber) is coated with the secondconductive metal (e.g., zinc or magnesium).

In practice, silver-coated polymer fibers manufactured by Noble FiberTechnologies, Inc. (Clarks Summit, Pa.) may be coated with zinc usingmethods such as conductive zinc ink printing, electroplating,electroless deposition, vacuum deposition, and spray coating.Alternatively, a metallic zinc or magnesium particulate (e.g., bead orthin wire) may be coated at one end or at certain portions) withsilver-silver oxide or silver-silver chloride. Spherical ornon-spherical particles with an average particle size ranging from aboutone micrometer to about 5 millimeters may be partially covered with thefirst and second conductive metal coatings in a similar fashion.

The coating methods for such first and second conductive metals inpreparing the galvanic couples may be electroless deposition, electricplating, vacuum vapor deposition, arc spray, conductive metal ink, andother known metal coating methods commonly used in electronic andmedical device manufacturing processes. The galvanic couple particulatesare preferably stored in aforementioned anhydrous forms, e.g., as a drypowder or immobilized in a fabric with binding agents, or as anessentially anhydrous non-conducting organic solvent composition (e.g.,dissolved in polyethylene glycols, propylene glycol, glycerin, liquidsilicone, and/or alcohol). The galvanic particulates have greatversatility in applications, and can be used in many consumer andmedical products such as patches, bandages, masks, garments, cloths,socks, bed sheets (e.g., by immobilized into the carrier or fabric),spread-on facial mask composition (such as a paste, cream or gel),creams, lotions, gels, shampoos, cleansers, powders, or incorporatedinto personal and medical products such as toothbrushes, dental flosses,wound dressings, diapers, sanitary napkins, dry wipes, pre-moisturedwipes (with aforementioned anhydrous solvents), tampons, and rectal andvaginal suppositories. The galvanic particulates may also beincorporated into transdermal drug delivery patches to enhance drugpenetration into the skin by iontophoresis and to reduce skin irritationby electric stimulation and electrically generated beneficial ions suchas zinc ions.

EXAMPLE 1 Carriers

Examples of several carriers, including the weight percentage range ofthe ingredients of such carriers, are set forth in Table 1.

TABLE 1 Percent by Weight of the Carrier Component No. 1 No. 2 No. 3 No.4 No. 5 No. 6 Salicylic acid 0.1–10   2 2 0 0 0.1– 10 Benzyl peroxide 00 0 0.5–10   0 0 Sulfur 0 0 0 0 3 3 Resorcinol 0 0 0 1 1 1 Benzalkonium0–2  0.1 0.1 0–2  0–2  0–2  chloride Benzethonium or 0–2  0 0 0–2  0–2 0–2  methylbezethonium chloride Cetylpyridium 0–2  0.1 0.1 0–2  0–2 0–2  chloride Phospholipid CDM 0–40 5 5 0–40 0–40 0–40 Hydrogen peroxide0–30 0 3 0–30 0–30 0–30 Buffer (citrate, 0–10 2 2 0–10 0–10 0–10lactate, or phosphate salts of sodium, potassium, or lithium Gellingagent 0–20 5 5 0–20 0–20 0–20 (e.g., polyacrylates, cellulose, naturalor synthetic gums, or polyacrylamide) Chelating agent 0–2  0.1 0.1 0–2 0–2  0–2  (e.g., EDTA) Propylene glycol 0–30 20 15 0–30 0–30 0–30Polyethylene 0–50 0 0 0–50 0–50 0–50 glycol Polypropylene 0–40 0 0 0–400–40 0–40 glycol Ethyl alcohol 0–50 0 15 0–50 0–50 0–50 Isopropylalcohol 0–50 0 0 0–50 0–50 0–50 Dimethyl 0–20 2 0 0–20 0–20 0–20isosorbide Isopropyl 0–30 1 1 0–30 0–30 0–30 myristate Purified water Qsto Qs to Qs to Qs to Qs to Qs to 100 100 100 100 100 100

In order to evaluate the proposed mechanism of action for theelectrochemically generated beneficial agents, an in vitro microbiologicstudy was conducted to investigate effect of electrolysis on P. acneinhibition in certain electrochemical systems; and an in vivo study wasconducted in human volunteers using a commercial iontophoresis device.

EXAMPLE 2 In vitro Inhibition of P. acnes by Electrolysis

A BacT/ALERT system (BioMerieux, Inc., Durham, N.C.) was used in the P.acnes inhibition experiment. Briefly, 40 ml of an anaerobic casein andsoy based broth culture medium in a bottle (BacT/ALERT SN, OrganonTekniks Corp., Durham, N.C.) was inoculated with P. acnes. The fullyautomated BacT/ALERT system was used to detect P. acnes growth over a14-day study at 35° C. by continuous monitoring of CO₂ production usingan optical colorimetric sensory system. A selected pair of theelectrodes (Table 2, Columns 2 and 3) was disinfected with 70% isopropylalcohol, and inserted through the rubber stopper into the culture mediumin a nitrogen glove box. Some electrodes were connected to the poles ofa battery (either 1.5 or 3V as indicated in Table 2, Column 3) for 30minutes. The electrodes were then immediately removed from theBacT/ALERT bottle, which was then placed into the automated incubationand monitoring system for two weeks. Other elecrodes (i.e., Nos. 3 & 5in Table 2), were not connected to an external battery, but rather weredirectly connected to each other at their ends outside the BacT/ALERTbottle to form galvanic couple. The electrodes of these galvanic couples(i.e., Nos. 3 & 5) remained in contact with the culture medium in thebottle during the 14-day study.

Zinc as the positive electrode (anode), with various materials as thenegative electrode (cathode), was evaluated through the test conditions1 to 7 (No. 1–7 in Column 1). Column 4 shows the voltage applied to theconductive electrode by the external battery. However, by simplyconnecting two conductive electrode materials, a voltage was alsogenerated just from the galvanic pair. For example, zinc-silver/silverchloride galvanic couple has a voltage of 0.9849V or about 1V (Zn²⁺+2e⁻=Zn, standard potential: −0.7626V, and AgCl+e⁻=Ag+Cl⁻, standardpotential: 0.2223V) and zinc-copper galvanic couple has a voltage ofabout 1.1–1.3V (Cu²⁺+2e⁻=Cu, standard potential: 0.340V, and Cu++e⁻=Cu,standard potential: 0.520V) Reference: Electrochemistry Handbook, 1995,Table 14.1, McGraw-Hill, Inc. New York, N.Y.).

In the test condition No. 7, the electrodes (i.e., zinc-silver/silverchloride galvanic couple) were taken from a commercial iontophoresisdevice (IontoPatch, SP, Birch Point Medical, Inc., Oakdale, Minn.). TheIontoPatch is an iontophoresis device powered by a galvanic couple“battery strip” made of zinc and silver/silver chloride in abandage-like device. In this experiment, the “battery strip” in theIontoPatch was taken out of the bandage-like device, and placed into theBacT/ALERT bottle. The electrodes of the commercial zinc-silver/silverchloride galvanic couple (No. 7) remained in the BacT/ALERT bottlethrough out the entire two-week experiments. Test conditions of Nos.15–17 were positive controls (i.e., without electrodes): Test conditionNo. 15 used a concentrated P. acne culture that was used to inoculatethe rest of the culture medium in each BacT/ALERT bottle to P. acnescounts of 10⁶ per ml and Test conditions No. 16 and No. 17 used theinoculated culture medium of P. acnes counts of 10⁶ per ml (with therubber stoppers of No. 16 additionally being punctured in a way similarto the rest of electrode-tested conditions in order to eliminate anyfalse P. acnes inhibition results due to potential environmental oxygenentry into the test bottle and affecting anaerobic P. acnes growth).

TABLE 2 Voltage applied by Average connected time to to a PositiveNumber battery P. acnes positive/ Positive Negative or Growth number No.Electrode Electrode batteries (days) tested 1 Zinc Silver/Silver 3 V —0/3 Chloride 2 Zinc Zinc 3 V — 0/1 3 Zinc Copper None^(a) — 0/2 4 ZincCopper 1.5 V   — 0/1 5 Zinc Silver/Silver None^(a) — 0/2 Chloride 6 ZincSilver/Silver 1.5 V   — 0/2 Chloride 7 Zinc Silver/Silver None^(a) —^(b)2/6 Chloride 8 Copper Silver/Silver 3 V — 0/3 Chloride 9 Copper Copper 3V — 0/2 10 Platinum Silver/Silver 3 V 1.6 2/2 Chloride 11 PlatinumPlatinum 3 V 1.1 1/1 12 Silver Silver/Silver 3 V 5.7^(c) 2/3 Chloride 13Silver Silver 3 V 2.8d 2/2 14 Silver/ Silver/Silver 3 V 3.0 2/2 SilverChloride Chloride 15 None None None 0.8 2/2 16 None None None 1.4 2/2 17None None None 1.3 2/2 ^(a)The conductive metal electrodes were notconnected to any battery, but to each other. Therefore, there is avoltage across the two electrode dictated by the galvanic pair. ^(b)Atotal of 6 samples were tested; 4 negative and 2 positive (0.6d & 0.8d);the positive ones were very likely due to bacterial contamination sincethey were detected faster then the positive control samples (Nos. 16 &17), and therefore were omitted. ^(c)Out of 3 samples, two positive(4.1d & 7.3d) were averaged

The zinc anode was surprisingly found to almost completely inhibit P.acne growth during the 14-day incubation study at the all of the voltageconditions tested (Nos. 1–7; in No. 7, two of the six commercialgalvanic couples showed positive P. acnes growth probably due bacterialcontamination, see Note C of Table 2). The copper anode was also foundto significantly inhibit P acnes growth (Nos. 8–9). Under theseexperimental conditions, the platinum anode showed little P. acneinhibition effect and the silver or silver/silver chloride anodesprovided only a weak P. acne inhibition. Since all the positive controlconditions (Nos. 15–17) showed positive P. acnes growth less than twodays after the beginning of the study, the negative P. acnes growth canbe attributed to the inhibition effect of the electrochemicallygenerated species or electric current passage through the culturemedium. Because electric current passage in Nos. 10–14 failed to showstrong P. acnes inhibition as those in Nos. 1–9, the observed bacterialinhibition in Nos. 1–9 were likely due to certain electrochemicalreactions occurred at the anode, namely, when zinc and copper were usedas the anode. It was also unexpected that the silver ions released fromsilver or silver/silver chloride anode under these experimentalconditions failed to show the same P. acnes inhibition (Nos. 12–14),since silver ion is well-known anti-microbial agent. See. e.g.,Spacciapoli et al. (“Antimicrobial activity of silver nitrate againstperiodontal pathogens.”, J Periodontal Res 36: 2, 108–13, April, 2001).It was surprising that, in the absence of external battery (Nos. 3, 5and 7), a pair of electrodes of galvanic couple with zinc as anode weresufficient to inhibit P. acnes growth during the entire two week study.

EXAMPLE 3 In Vitro Electrode-Salicylic Acid Compatibility

The following experiment was conducted to determine the compatibility ofelectrodes with salicylic acid. A pair of test electrodes was immersedin 5 ml of 1.5% salicylic acid solution (solvent 50% ethanol/50% water).A pre-determined voltage was applied to the electrodes (by connectingthe electrodes to a battery or batteries) for certain length of time asindicated in Table 3. Observations were made on color change of the testsolution.

The solution with the zinc anode showed no discoloration, indicatinggood compatibility with salicylic acid during the passage of electriccurrent. Use of the platinum anode unexpectedly resulted indiscoloration, indicating incompatibility with salicylic acid under thisexperimental condition.

TABLE 3 Electrode Material Test Observation Anode Cathode VoltageDuration Solution color (+) (−) (V) (min) change Platinum Platinum 3 10Colorless → yellow Platinum Platinum 9 10 Colorless → brown ZincPlatinum 1.5 10 No color change Zinc Platinum 3 10 No color change ZincPlatinum 9 30 No color change

EXAMPLE 4 In Vivo Human Iontophoresis Study

An in vivo study was conducted in human volunteers using a commercialiontophoresis device (IontoPatch®, Model: SP, Birch Point Medical Inc.,North Oakdale, Minn.). The study recruited the healthy female volunteerswith oily skin, aged from 20–45 years. The sebumeter reading from eachsubject's forehead was at least greater than 150 mg/cm²/hr. The studywas blind and controlled. Briefly, an IontoPatch® with a voltage of 1volt, an operating current of 0.06 mA, and an active treatment area of1.25 in², was applied to the treatment site of the human subject (e.g.forehead). The positive electrode and negative consisted of zinc andsilver/silver chloride (Ag/AgCl)material, respectively. Both electrodeswere filled with saline (0.9% NaCl). As soon as the saline solution wasadded into the different electrodes, the electric patch begin tofunction. The patch was left on the treatment area overnight (e.g.,approximately 8 hours).

The following evaluations were conducted: (i) the effects ofelectrolysis on the skin condition were monitored using a normalphotography and (ii) The change in p. acnes counts was determinedthrough analyzing the cup wash solution for the treatment site beforeand after wearing the patch overnight. The cup wash micro samplingprocedure was performed as follows: a cylindrical cup (2.1 cm diameterand 2.5 cm height) having two open ends was fastened onto the treatmentarea. The treatment area inside the cylinder was then washed with 2 mlof cleansing buffer (sterile 0.075M Phosphate Buffer containing 0.1%Triton X-100) while the same area with a sterile polished glass. Thewash solution was then collected. This washing procedure was thenrepeated. The two collected samples were pooled and used in the P-acnesanalysis.

The P. acnes counts were determined by Spiral Plating the scrub samplesanaerobically in Actinomyces Agar for 5 days, and the predominantcontaminants on the spiral plates were Gram stained and identified usingthe VITEK System. Using an automated colony counter, the P-acne countper mL of each sample buffer was determined.

After only one overnight patch application, P. acne quantificationmeasurement on the treatment area shows a 45% P. acne reduction relativeto the baseline under the zinc anode and 30% under the Ag/AgCl cathode.After four consecutive overnight patch applications, photo imagesdisplayed the clear evidences of significant reduction in the color andsize of post-acne hyperpigmentation spot under the zinc electrode. Thistest subject had a post-acne hyperpigmentation spot at the test skinsite. The appearance of the hyperpigmented spot was improved from a verydark color to a lighter color.

Also, after four consecutive overnight patch applications, photo imagesalso displayed the evidence of significant reduction in the color andsize of an acne pimple under the Ag/AgCl electrode. This test subjecthad an acne pimple at the test skin site. The redness of the pimple wasrapidly reduced from very red color to become almost invisible while thepimples at the non-treated skin area remained largely unchanged.

EXAMPLE 5 In Vivo Human Iontophoresis Study Using HistamineHydrochloride as Marker

An in vivo study was conducted in three human volunteers using agalvanic zinc-silver/silver oxide device to deliver histaminehydrochloride as a marker into the skin. Histamine-induced skin erythemaand itchiness were recorded during and after the study. The studyrecruited two healthy male and one female volunteers with ages ranging41 to 49 years. The galvanic devices were prepared by cutting a thinzinc foil (0.25 mm thick, Alfa Aesar, Word Hill, Mass.) into rectangularpiece (2.5 cm wide & 3 cm long). A silver ink (Silver Print, M.G.Chemicals, Toronto, Ontario, Canada) was painted onto one side of thezinc foil as a 0.5 cm wide stripe along the long-axis at the center. Theink was air-dried to produce the silver electrode stripe on the zincfoil. Two rectangular adhesive Scotch® tape stripes of 0.5 cm wide and 3cm long were placed on the both sides of the silver electrode stripecreating an electric insulating gap on the surface (electrode gap=0.5cm). A rectangular piece of nonwoven fabric (50% Rayon/50% PET, 75 gsm,PGI Polymer Group Inc., Landisville, N.J.) of 3 cm wide and 3.5 cm longwas placed over the zinc-silver electrode side of the zinc foil. Arectangular adhesive backing film of 4 cm wide and 5 cm long was affixedto the opposite side of the zinc foil to complete the zinc-silvergalvanic device.

A second type of the zinc-silver galvanic device without and electricinsulating gap on the surface (electrode gap=0 cm) was prepared bysimply omitting the addition of the adhesive Scotch® tape. A third type(control) patch was prepared by using only the zinc foil, the nonwovenpad, and the adhesive backing film to construct the device.

To begin histamine iontophoresis, 0.8 ml aqueous solution of 0.1%histamine hydrochloride (Sigma-Aldrich, St. Louis, Mo.) was added toeach device, which was then affixed to the forearm skin of eachvolunteer for 30 minutes.

At the end of the study, red spots (histamine induced erythema) appearedunder both zinc-silver galvanic patch devices, which disappeared withinabout one half hour. A close examination showed the red spots around thehair follicles. There was also itchiness reported at the galvanic patchsites reported during the patch application. In contrast, there were nochange in skin color under, nor any itchiness reported with, the controlpatch devices.

EXAMPLE 6 In Vivo Human Iontophoresis Study Using HistamineHydrochloride with a Galvanic Nose Patch Comprising Zinc Mesh

As a continuation of the human in vivo study in the previous example, agalvanic patch device (designated here as “Test Device D”) comprising azinc mesh (diamond openings of 1 cm long & 0.4 cm wide, DexmetCorporation, Naugatuck, Conn.) instead of zinc foil was prepared withthe same dimension and procedure as the galvanic device (gapelectrode=0) in EXAMPLE 5. The device thus prepared resembled to thedesign shown in FIG. 11 with three parallel electrodes: the silverelectrode in the center and zinc electrodes on both sides. Two malevolunteers participated this study using a similar test conditions as inEXAMPE 5. One Test Device containing 0.8 ml of 0.1% histaminehydrochloride was applied to the nose of each volunteer for 30 minutes.Itchiness was reported within 5 minutes of the nose patch application,indicating rapid delivery of histamine into the relatively larger skinpores on the nose. For both test subjects, pronounced erythema wasobserved at the skin site under the nose patch after patch removal atthe end of the study, in comparison to the study conducted on theforearm skin.

It is understood that while the invention has been described inconjunction with the detailed description thereof, that the foregoingdescription is intended to illustrate and not limit the scope of theinvention, which is defined by the scope of the appended claims. Otheraspects, advantages, and modifications are within the claims.

1. A method of treating acne or rosacea on the skin, said method comprising applying electricity to skin in need of such treatment wherein said electricity is generated by a first conductive electrode in electric communication with a second conductive electrode, wherein both said first conductive electrode and said second conductive electrode are in ionic communication with said skin, wherein the difference of the standard potentials of said first conductive electrode and said second conductive electrode is at least 0.2 V and wherein the electrons that pass between said first conductive electrode and said second conductive electrode are generated as a result of said difference of the standard potentials, wherein said method comprises applying to said skin a device comprising: a housing having a skin contacting surface; said first conductive electrode; said second conductive electrode; and a carrier; wherein said first conductive electrode and said second conductive electrode are in ionic communication with said carrier and wherein said carrier is in communication with said skin through said skin contacting surface, and wherein said device is adapted to be affixed to said skin and to deliver electric current from said first conductive electrode, through said carrier, through said skin, and through said carrier to said second conductive electrode.
 2. A method of claim 1, wherein said first conductive electrode comprises zinc.
 3. A method of claim 2, wherein carrier is added to said device by the user prior to application to said skin.
 4. A method of claim 3, wherein said carrier further comprises an anti-acne agent selected from the group comprising tretinoin, isotretinoin, motretinide, adapalene, tazarotene, azelaic acid, retinol, salicylic acid, benzoyl peroxide, resorcinol, sulfur, sulfacetamide, tetracycline, clindamycin, metronidazole, erythromycin, and salts thereof.
 5. A method of claim 2, wherein said housing is a non-woven substrate.
 6. A method of claim 5, wherein carrier is added to said device by the user prior to application to said skin.
 7. A method of claim 6, wherein said carrier further comprises an anti-acne agent selected from the group comprising tretinoin, isotretinoin, motretinide, adapalene, tazarotene, azelaic acid, retinol, salicylic acid, benzoyl peroxide, resorcinol, sulfur, sulfacetamide, tetracycline, clindamycin, metronidazole, erythromycin, and salts thereof.
 8. A method of claim 5, wherein said carrier further comprises an anti-acne agent selected from the group comprising tretinoin, isotretinoin, motretinide, adapalene, tazarotene, azelaic acid, retinol, salicylic acid, benzoyl peroxide, resorcinol, sulfur, sulfacetamide, tetracycline, clindamycin, metronidazole, erythromycin, and salts thereof.
 9. A method of claim 2, wherein said carrier further comprises an anti-acne agent selected from the group comprising tretinoin, isotretinoin, motretinide, adapalene, tazarotene, azelaic acid, retinol, salicylic acid, benzoyl peroxide, resorcinol, sulfur, sulfacetamide, tetracycline, clindamycin, metronidazole, erythromycin, and salts thereof.
 10. A method of claim 1, wherein said housing is a non-woven substrate.
 11. A method of claim 10, wherein said carrier further comprises an anti-acne agent selected from the group comprising tretinoin, isotretinoin, motretinide, adapalene, tazarotene, azelaic acid, retinol, salicylic acid, benzoyl peroxide, resorcinol, sulfur, sulfacetamide, tetracycline, clindamycin, metronidazole, erythromycin, and salts thereof.
 12. A method of claim 10, wherein said carrier further comprises an anti-acne agent selected from the group comprising tretinoin, isotretinoin, motretinide, adapalene, tazarotene, azelaic acid, retinol, salicylic acid, benzoyl peroxide, resorcinol, sulfur, sulfacetamide, tetracycline, clindamycin, metronidazole, erythromycin, and salts thereof.
 13. A method of claim 1, wherein carrier is added to said device by the user prior to application to said skin.
 14. A method of claim 13, wherein said carrier further comprises an anti-acne agent selected from the group comprising tretinoin, isotretinoin, motretinide, adapalene, tazarotene, azelaic acid, retinol, salicylic acid, benzoyl peroxide, resorcinol, sulfur, sulfacetamide, tetracycline, clindamycin, metronidazole, erythromycin, and salts thereof.
 15. A method of treating acne or rosacea on the skin, said method comprising applying electricity to skin in need of such treatment wherein said electricity is generated by a first conductive electrode that is an anode in electric communication with a second conductive electrode that is a cathode, wherein both said first conductive electrode and said second conductive electrode are in ionic communication with said skin, wherein the difference of the standard potentials of said first conductive electrode and said second conductive electrode is at least 0.2 V and wherein the electrons that pass between said first conductive electrode and said second conductive electrode are generated as a result of said difference of the standard potentials, wherein said method comprises, wherein said method comprises topically applying a composition to said skin, said composition comprising said first conductive electrode in the form of a particulate and a second conductive electrode partially coated on said particulate.
 16. A method of claim 15, wherein said first conductive electrode comprises zinc and said second conductive electrode comprises silver.
 17. A method of claim 15, wherein said composition further comprises an anti-acne agent selected from the group comprising tretinoin, isotretinoin, motretinide, adapalene, tazarotene, azelaic acid, retinol, salicylic acid, benzoyl peroxide, resorcinol, sulfur, sulfacetamide, tetracycline, clindamycin, metronidazole, erythromycin, and salts thereof. 